Assays for Insulin and Insulin-Like Signal Transduction Based on Adipocytes, Hepatocytes, and Myocytes

  • Günter Müller
Living reference work entry


After having established insulin-like activity of compounds/drug candidates in primary or cultured adipose, muscle, and liver cells or tissues with one or several of the metabolic assays described above (see K.6.1 and K.6.2), it is often useful to elucidate the molecular mode of action of these compounds/drug candidates for further characterization and optimization, in particular regarding selectivity and potency. For this, detailed knowledge in the molecular mechanisms of the insulin signal transduction cascade as well as of cross-talking insulin-like signaling pathways as well as the availability of appropriate reliable and robust cell-free and cell-based assays reflecting these events is required. The following view results from the current experimental findings but, due to limitations in space and rapid progress still made in this area, has to be considered as simplified and temporary, only.


Lipid Raft High Pressure Liquid Chromatography Fluorescence Resonance Energy Transfer Protein Tyrosine Phosphatase Scintillation Proximity Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Further Reading

Bacterial Cell-Based Assay

  1. Alessi DR, Downes CP (1998) The role of PI 3-kinase in insulin action. Biochim Biophys Acta 1436:151–164PubMedGoogle Scholar
  2. Alonso A, Sasin J, Bottini N, Osterman A, Godzik A, Hunter T, Dixon J, Mustelin T (2004) Protein tyrosine phosphatases in the humane genome. Cell 117:699–711PubMedGoogle Scholar
  3. Andersen JN, Mortensen OH, Peters GH, Drake PG, Iversen LF, Olsen OH, Jansen PG, Andersen HS, Tonks NK, Moller NP (2001) Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol 21:7117–7136PubMedCentralPubMedGoogle Scholar
  4. Andersson L, Porath J (1986) Isolation of phosphoproteins by immobilized metal (Fe2+) affinity chromatography. Anal Biochem 155:250–254Google Scholar
  5. Angeles TS, Steffler C, Bartlett BA, Hudkins RL, Stephens RM, Kaplan DR, Dionne CA (1996) Enzyme-linked immunosorbent assay for trkA tyrosine kinase activity. Anal Biochem 236:49–55PubMedGoogle Scholar
  6. Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, Bouvier M (2000) Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc Natl Acad Sci U S A 97:3684–3689PubMedCentralPubMedGoogle Scholar
  7. Antonsson B, Marshall CJ, Montessuit S, Arkinstall S (1999) An in vitro 96-well plate assay of the mitogen-activated protein kinase cascade. Anal Biochem 267:294–299PubMedGoogle Scholar
  8. Arai R (2000) Fluorolabeling of antibody variable domains with green fluorescent protein variants: application to an energy transfer-based homogeneous immunoassay. Protein Eng 13:369–376PubMedGoogle Scholar
  9. Arai R (2001) Demonstration of a homogeneous noncompetitive immunoassay based on bioluminescence resonance energy transfer. Anal Biochem 289:77–81PubMedGoogle Scholar
  10. Argetsinger LS, Hsu GW, Myers MG Jr, Billestrup N, White MF, Carter-Su C (1995) Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J Biol Chem 270:14685–14692Google Scholar
  11. Aronheim A, Engelberg D, Li N, al-Alawi N, Schlessinger J, Karin M (1994) Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell 78:949–961PubMedGoogle Scholar
  12. Aronheim A, Broder YC, Cohen A, Fritsch A, Belisle B, Abo A (1998) Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. Curr Biol 8:1125–1128PubMedGoogle Scholar
  13. Barberis A (2002) Cell-based high-throughput screens for drug discovery. Eur Biopharm Rev Winter:93–96Google Scholar
  14. Barford D, Keller JC, Flint AJ, Tonks NK (1994) Purification and crystallization of the catalytic domain of human protein tyrosine phosphatase 1B expressed in Escherichia coli. J Mol Biol 239:726–730PubMedGoogle Scholar
  15. Barford D, Das AK, Egloff MP (1998) The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct 27:133–164PubMedGoogle Scholar
  16. Baron V, Calleja V, Ferrari P, Alengrin F, Van Obberghen E (1998) pp125FAK focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors. J Biol Chem 273:7162–7166PubMedGoogle Scholar
  17. Biazzo-Ashnault DE, Park Y-W, Cummings RT, Ding V, Moller DE, Ahang BB, Quershi SA (2001) Detection of insulin receptor tyrosine kinase activity using time-resolved fluorescence energy transfer technology. Anal Biochem 291:155–158PubMedGoogle Scholar
  18. Biddinger SB, Kahn CR (2006) From mice to men: insights into the insulin resistance syndromes. Annu Rev Physiol 68:123–158PubMedGoogle Scholar
  19. Blero D, De Smedt F, Pesesse X, Paternotte N, Moreau C, Payrastre B, Erneux C (2001) The SH2 domain containing inositol 5-phosphatase SHIP2 controls phosphatidylinositol 3,4,5-trisphosphate levels in CHO-IR cells stimulated by insulin. Biochem Biophys Res Commun 282:839–843PubMedGoogle Scholar
  20. Blero D, Zhang J, Pesesse X, Payrastre B, Dumont JE, Schurmans S, Erneux C (2005) Phosphatidyl 3,4,5-trisphosphate modulation in SHIP2-deficient mouse embryonic fibroblasts. FEBS J 272:2512–2522PubMedGoogle Scholar
  21. Bourdeau A, Dube N, Tremblay ML (2005) Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP. Curr Opin Cell Biol 17:203–209PubMedGoogle Scholar
  22. Boute N, Pernet K, Isaad T (2001) Monitoring the activation state of the insulin receptor using bioluminescence resonance energy transfer. Mol Pharmacol 60:640–645PubMedGoogle Scholar
  23. Boute N, Jockers R, Issad T (2002) The use of resonance energy transfer in high-throughput screening: BRET versus FRET. Trends Pharmacol Sci 23:351–354PubMedGoogle Scholar
  24. Braun S, Raymond WE, Racker E (1984) Synthetic tyrosine polymers as substrates and inhibitors of tyrosine-specific protein kinases. J Biol Chem 259:2051–2054PubMedGoogle Scholar
  25. Braunwalder AF, Yarwood DR, Hall T, Missbach M, Lipson KE, Sills MA (1996) A solid phase assay for the determination of protein tyrosine kinase activity of c-src using scintillation microtitration plates. Anal Biochem 234:23–26Google Scholar
  26. Bravo J, Karathanassis D, Pacold CM, Pacold ME, Ellson CD, Anderson KE, Butler PJ, Lavenir I, Perisic PT, Hawkins L, Stephens L, Williams RL (2001) The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate. Mol Cell 8:829–839PubMedGoogle Scholar
  27. Broder YC, Katz S, Aronheim A (1998) The ras recruitment system, a novel approach to the study of protein-protein interactions. Curr Biol 8:1121–1124PubMedGoogle Scholar
  28. Brugge JS, Jarosik G, Andersen J, Queral-Lustig A, Fedor-Chaiken M, Broach JR (1987) Expression of Rous sarcoma virus transforming protein pp60v-src in Saccharomyces cerevisiae cells. Mol Cell Biol 7:2180–2187PubMedCentralPubMedGoogle Scholar
  29. Brune M, Hunter JL, Corrie JET, Webb MR (1994) Direct, real-time measurement of rapid inorganic phosphate release using a novel fluorescent probe and its application to actomyosin subfragment 1 ATPase. Biochemistry 33:8262–8271PubMedGoogle Scholar
  30. Brune M, Hunter JL, Howell SA, Martin SR, Hazlett TL, Corrie JET, Webb MR (1998) Mechanism of inorganic phosphate interaction with phosphate binding protein from Escherichia coli. Biochemistry 37:10370–10380PubMedGoogle Scholar
  31. Cheatham RB, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR (1994) Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70S6 kinase, DNA synthesis, and glucose transporter translocation. Mol Cell Biol 14:4902–4911PubMedCentralPubMedGoogle Scholar
  32. Chen PS, Toribara TY, Warner H (1956) Microdetermination of phosphorus. Anal Chem 28:1756–1758Google Scholar
  33. Cheng A, Dube N, Gu F, Tremblay ML (2002) Coordinated action of protein tyrosine phosphatases in insulin signal transduction. Eur J Biochem 269:1050–1059PubMedGoogle Scholar
  34. Clement S et al (2001) The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92–97PubMedGoogle Scholar
  35. Coffin J, Latev M, Bi X, Nikiforov TT (2000) Detection of phosphopeptides by fluorescence polarization in the presence of cationic polyamino acids: application to kinase assays. Anal Biochem 278:206–212PubMedGoogle Scholar
  36. Cohen CB, Chin-Dixon E, Jeong S, Nikiforov TT (1999) A microchip-based enzyme assay for protein kinase A. Anal Biochem 273:89–97PubMedGoogle Scholar
  37. Combettes-Souverain M, Isaad T (1998) Molecular basis of insulin action. Diabetes Metab 24:477–489PubMedGoogle Scholar
  38. Cromlish WA, Kennedy B (1996) Selective inhibition of cyclooxygenase-1 and −2 using intact insect cells assays. Biochem Pharmacol 52:1777–1785PubMedGoogle Scholar
  39. Cromlish WA, Payette P, Kennedy BP (1999) Development and validation of an intact cell assay for protein tyrosine phosphatases using recombinant baculoviruses. Biochem Pharmacol 58:1539–1546PubMedGoogle Scholar
  40. Cubitt AB (1995) Understanding, improving and using green fluorescent protein. Trends Biochem Sci 20:448–455PubMedGoogle Scholar
  41. Dass C, Mahalakshmi P (1996) Phosphorylation of enkephalins enhances their proteolytic stability. Life Sci 58:1039–1045PubMedGoogle Scholar
  42. Dawson JF, Boland MP, Holmes CFB (1994) A capillary electrophoresis-based assay protein kinases and protein phosphatases using peptide substrates. Anal Biochem 220:340–345PubMedGoogle Scholar
  43. DeMeyts P, Bianco AR, Roth J (1976) Site-site interactions among insulin receptors. Characterization of the negative cooperativity. J Biol Chem 251:1877–1888PubMedGoogle Scholar
  44. Ehrhard KN, Jacoby JJ, Fu XY, Jahn R, Dohlman HG (2000) Use of G-protein fusions to monitor integral membrane protein-protein interactions in yeast. Nat Biotechnol 18:1075–1079PubMedGoogle Scholar
  45. Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP (1999) Science 283:1544–1548PubMedGoogle Scholar
  46. Ellen Chan LP, Swaminathan R (1986) Adenosine triphosphate interferes with phosphate determination. Clin Chem 32:1981–1982Google Scholar
  47. Ellis L, Clauser E, Morgan DO, Edery M, Roth RA, Rutter WJ (1986) Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell 45:721–732PubMedGoogle Scholar
  48. Flint AJ, Gebbink MFBG, Franza BR, Hill DE, Tonks NK (1993) Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation. EMBO J 12:1937–1946PubMedCentralPubMedGoogle Scholar
  49. Flint AJ, Tiganis T, Barford D, Tonks NK (1997) Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases. Proc Natl Acad Sci U S A 94:1680–1685PubMedCentralPubMedGoogle Scholar
  50. Florio M, Wilson LK, Trager JB, Thorner J, Martin GS (1994) Aberrant protein phosphorylation at tyrosine is responsible for the growth-inhibitory action of pp60v-src expressed in the yeast Saccharomyces cerevisiae. Mol Biol Cell 5:283–296PubMedCentralPubMedGoogle Scholar
  51. Frick W, Bauer A, Bauer J, Wied S, Müller G (1998) Insulinmimetic signalling of synthetic phosphoinositolglycans in isolated rat adipocytes. Biochem J 336:163–181Google Scholar
  52. Funaki M, Katagiri H, Kanda A, Anai M, Nawano M, Ogihara K, Inukai Y, Fukushima H, Ono H (1999) p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring. J Biol Chem 274:22019–22024PubMedGoogle Scholar
  53. Gee KR, Sun WC, Bhalgat MK, Upson RH, Klaubert DH, Lataham KA, Haugland RP (1999) Fluorogenic substrates based on fluorinated umbelliferones for continuous assays of phosphatases and beta-galactosidases. Anal Biochem 273:41–48PubMedGoogle Scholar
  54. Geisen K (1988) Special pharmacology of the new sulfonylurea glimepiride. Drug Res 38:1120–1130Google Scholar
  55. Gillooly DJ, Simonsen A, Stenmark H (2001) Cellular functions of phosphatidylinositol 3-phosphate and FYVE domain proteins. Biochem J 355:249–258PubMedCentralPubMedGoogle Scholar
  56. Giuriato S, Pesesse X, Bodin S, Sasaki T, Viala C, Marion E, Penninger J, Schurmans S, Erneux C, Payrastre B (2003) SH2-containing inositol 5-phosphatases 1 and 2 in blood platelets. Their interactions and roles in the control of phosphatidylinositol 3,4,5-trisphosphate levels. Biochem J 376:199–207PubMedCentralPubMedGoogle Scholar
  57. Goddard J-P, Reymond J-L (2004) Enzyme assays for high-throughput screening. Curr Opin Biotechnol 15:314–322PubMedGoogle Scholar
  58. Gray A, Van Der Kaay J, Downes CP (1999) The pleckstrin homology domains of protein kinase b- and GRP1 (general receptor for phosphoinositides-1) are sensitive and selective probes for the cellular detection of phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 3,4,5-trisphosphate in vivo. Biochem J 344:929–936PubMedCentralPubMedGoogle Scholar
  59. Gray A, Olsson H, Batty IH, Priganica L, Downes CP (2003) Nonradioactive methods for the assay of phosphoinositide 3-kinases and phosphoinositide phosphatases and selective detection of signaling lipids in cell and tissue extracts. Anal Biochem 313:234–245PubMedGoogle Scholar
  60. Gunde T (2004) In vivo veritas? Cell-based assays for identifying RTK inhibitors. Eur Biopharm Rev Spring:56–60Google Scholar
  61. Gunde T, Barberis A (2005) Yeast growth selection system for detecting activity and inhibition of dimerization-dependent receptor tyrosine kinase. Biotechniques 39:541–549PubMedGoogle Scholar
  62. Gustafson TA, Moodie SA, Lavan BE (1998) The insulin receptor and metabolic signaling. In: Reviews physiology, biochemistry and pharmacology, vol 137. Springer, Berlin/Heidelberg/New York, pp 71–192. The insulin receptor and metabolic signalingGoogle Scholar
  63. Hammonds TR, Maxwell A, Jenkins JR (1998) Use of a rapid throughput in vivo screen to investigate inhibitors of eukaryotic topoisomerase II enzymes. Antimicrob Agents Chemother 42:889–894PubMedCentralPubMedGoogle Scholar
  64. Herbst JJ, Andrews GC, Contillo LG, Singleton PH, Genereux PE, Gibbs EM, Lienhard GE (1995) Effect of the activation of phosphatidylinositol 3-kinase by a thiophosphotyrosine peptide on glucose transport in 3T3-L1 adipocytes. J Biol Chem 270:26000–26005PubMedGoogle Scholar
  65. Hjøllund E (1991) Insulin receptor binding and action in human adipocytes. Dan Med Bull 38:252–270PubMedGoogle Scholar
  66. Holman GD, Kasuga M (1997) From receptor to transporter: insulin signalling to glucose transport. Diabetologia 40:991–1003PubMedGoogle Scholar
  67. Hovius R (2000) Fluorescence techniques: shedding light on ligand-receptor interactions. Trends Pharmacol Sci 21:266–273PubMedGoogle Scholar
  68. Hresko RC, Mueckler M (2006) mTOR/RICTOR is the Ser473 kinase for Akt/PKB in 3T3-L1 adipocytes. J Biol Chem, in pressGoogle Scholar
  69. Huang Z, Wang Q, Ly HD, Govindarajan A, Scheigetz J, Zamboni R, Desmarais S, Ramachandran C (1999) 3,6-Fluorescein diphosphate: a sensitive fluorogenic and chromogenic substrate for protein tyrosine phosphatases. J Biomol Screen 4:327–334PubMedGoogle Scholar
  70. Huang W, Zhang Y, Sportsman JR (2002) A fluorescence polarization assay for cyclic nucleotide phosphodiesterases. J Biol Mol Screen 7:215–222Google Scholar
  71. Hubbard SR (1997) Crystal structure of the activated tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J 16:5572–5581PubMedCentralPubMedGoogle Scholar
  72. Hubsman M, Yudkovsky G, Aronheim A (2001) A novel approach for the identification of protein-protein interaction with integral membrane proteins. Nucleic Acids Res 29:E18PubMedCentralPubMedGoogle Scholar
  73. Hughes TR (2002) Yeast and drug discovery. Funct Integr Genomics 2:199–211PubMedGoogle Scholar
  74. Huppertz C, Schwartz C, Becker W, Horn F, Heinrich PC, Joost H-G (1996) Comparison of the effects of insulin, PDGF, interleukin-6, and interferon-y on glucose transport in 3T3-L1 cells: lack of cross-talk between tyrosine kinase receptors and JAK/STAT pathways. Diabetologia 39:1432–1439PubMedGoogle Scholar
  75. Hwang KJ (1976) Interference of ATP and acidity in the determination of inorganic phosphate by the Fiske and Subbarow method. Anal Biochem 75:40–44PubMedGoogle Scholar
  76. Itaya K, Ui M (1966) A new micromethod for the colorimetric determination of inorganic phosphate. Clin Chim Acta 14:361–366PubMedGoogle Scholar
  77. Jeong S, Nikiforov TT (1999) A kinase assay based on thiophosphorylation and biotinylation. Biotechniques 27:1232–1238PubMedGoogle Scholar
  78. Jiang G, Zhang BB (2002) PI 3-kinase and its up- and down- stream modulators as potential targets for the treatment of type II diabetes. Front Biosci 7:d902–d907Google Scholar
  79. Johnson TO, Ermolieff J, Jirousek MR (2002) Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Dis 1:696–709Google Scholar
  80. Kaiser C, Michaelis S, Mitchell A (1994) Methods in yeast genetics. CSH Laboratory Press, Cold Spring HarborGoogle Scholar
  81. Kessler A, Müller G, Wied S, Crecelius A, Eckel J (1998) Signalling pathways of an insulin-mimetic phosphoinositolglycan peptide in muscle and adipose tissues. Biochem J 330:277–286PubMedCentralPubMedGoogle Scholar
  82. Kirkbright GF, Narayanaswamy R, West TS (1972) The spectrofluorimetric determination of orthophosphate as quinine molybdophosphate. Analyst 97:174–181Google Scholar
  83. Kohler F, Müller KM (2003) Adaptation of the Ras-recruitment system to the analysis of interactions between membrane associated proteins. Nucleic Acids Res 31:e28PubMedCentralPubMedGoogle Scholar
  84. Kornbluth S, Jove R, Hanafusa H (1987) Characterization of avian and viral p60src proteins expressed in yeast. Proc Natl Acad Sci U S A 84:4455–4459PubMedCentralPubMedGoogle Scholar
  85. Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C (1996) Gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 and its association with Grb2 and the phosphatidylinositol 3-kinase. J Biol Chem 271:26356–26361PubMedGoogle Scholar
  86. Kristjansdottir K, Rudolph J (2003) A fluorescence polarization assay for native protein substrates of kinases. Anal Biochem 316:41–49PubMedGoogle Scholar
  87. Krutzfeldt J, Grunweller A, Raasch W, Drenckhan M, Klein HH (1999) Microtiter well assays for protein tyrosine phosphatase activities directed against phosphorylated insulin receptor or insulin receptor substrate-1. Anal Biochem 271:97–99PubMedGoogle Scholar
  88. Kupcho K, Somberg R, Bulleit B, Goueli SA (2003) A homogeneous, nonradioactive high-throughput fluorogenic protein kinase assay. Anal Biochem 317:210–217PubMedGoogle Scholar
  89. Kurlawalla-Martinez C (2005) Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Mol Cell Biol 25:2498–2510PubMedCentralPubMedGoogle Scholar
  90. Lemmon MA, Ferguson KM (2001) Molecular determinants in pleckstrin homology domains that allow specific recognition of phosphoinositides. Biochem Soc Trans 29:377–384PubMedGoogle Scholar
  91. Leon Y, Varela-Nieto I (2004) Glycosyl-phosphatidylinositol cleavage products in signal transduction. In: Müller G, Petry S (eds) Lipases and phospholipases in drug development. Wiley-VCH, Weinheim, pp 101–119Google Scholar
  92. Lin S, Fischl AS, Bi X, Parce W (2003) Separation of phospholipids in microfluidic chip device: application to high throughput screening assays for lipid-modifying enzymes. Anal Biochem 314:97–107PubMedGoogle Scholar
  93. Liu G, Trevillyan JM (2002) Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr Opin Invest Drugs 11:1608–1616Google Scholar
  94. Lorenzen JA, Dadabay CY, Fischer EH (1995) COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol 131:631–643PubMedGoogle Scholar
  95. Melese T, Hieter P (2002) From genetics and genomics to drug discovery: yeast rises to the challenge. Trends Pharmacol Sci 23:544–547PubMedGoogle Scholar
  96. Montalibet J, Kennedy BP (2004) Using yeast to screen for inhibitors of protein tyrosine phosphatase 1B. Biochem Pharmacol 68:1807–1814PubMedGoogle Scholar
  97. Müller G (2000a) The molecular mechanism of the insulinmimetic/sensitizing activity of the anti-diabetic sulfonylurea drug amaryl. Mol Med 6:907–933PubMedCentralPubMedGoogle Scholar
  98. Müller G, Geisen K (1996) Characterization of the molecular mode of action of the sulfonylurea, glimepiride, at adipocytes. Horm Metab Res 28:469–487PubMedGoogle Scholar
  99. Müller G, Wied S, Wetekam E-M, Crecelius A, Unkelbach A, Punter J (1994a) Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulfonylureas, glimepiride and glibenclamide, is correlated with modulations of the cAMP regulatory cascade. Biochem Pharmacol 48:985–996PubMedGoogle Scholar
  100. Müller G, Satoh Y, Geisen K (1995) Extrapancreatic effects of sulfonylureas – a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract 28(Suppl):S115–S137PubMedGoogle Scholar
  101. Müller G, Wied S, Crecelius A, Kessler A, Eckel J (1997) Phosphoinositolglycan-peptides from yeast potently induce metabolic insulin actions in isolated rat adipocytes, cardiomyocytes, and diaphragms. Endocrinology 138:3459–3475PubMedGoogle Scholar
  102. Müller G, Schulz A, Wied S, Frick W (2005a) Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes. Biochem Pharmacol 69:761–780PubMedGoogle Scholar
  103. Murray PF, Hammerschmidt P, Samela A, Passeron S (1996) Peptide degradation: effect of substrate phosphorylation on aminopeptidasic hydrolysis. Int J Biochem Cell Biol 28:451–456Google Scholar
  104. Myers MG, White MF (1995) New frontiers in insulin receptor substrate signaling. Trends Endocrinol Metab 6:209–215PubMedGoogle Scholar
  105. Nakashima N et al (2000) The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J Biol Chem 275:12889–12895PubMedGoogle Scholar
  106. Okada Y, Yoshida M, Baba S, Shii K (1998) Development of vanadate sensitive human erythrocyte insulin receptor tyrosine phosphatase assay. Diabetes Res Clin Pract 41:157–163PubMedGoogle Scholar
  107. Ozawa T, Sato M, Sugawara M, Umezawa Y (1998) An assay method for evaluating chemical selectivity of agonists for insulin signaling pathways based on agonist-induced phosphorylation of a target peptide. Anal Chem 70:2345–2352PubMedGoogle Scholar
  108. Park Y-W, Cummings RT, Wu L, Zheng S, Cameron PM, Woods A, Zaller DM, Marcy AI, Hermes JD (1999) Homogeneous proximity tyrosine kinase assays: scintillation proximity assay versus homogeneous time-resolved fluorescence. Anal Biochem 289:94–104Google Scholar
  109. Pastula C, Johnson I, Beechem JM, Patton WF (2003) Development of fluorescence-based assays for serine/threonine and tyrosine phosphatases. Comb Chem High Throughput Screen 6:341–346PubMedGoogle Scholar
  110. Pedersen O, Hjøllund E, Beck-Nielsen H, Lindskov HO, Sonne O, Gliemann J (1981) Insulin receptor binding and receptor-mediated insulin degradation in human adipocytes. Diabetologia 20:636–641PubMedGoogle Scholar
  111. Pedersen O, Hjøllund E, Linkskov HO (1982) Insulin binding and action on fat cells from young healthy females and males. Am J Physiol 243:E158–E167PubMedGoogle Scholar
  112. Pesesse X, Dewaste V, De Smedt F, Laffargue M, Giuriato S, Moreau C, Payrastre B, Erneux C (2001) The Src homology 2 domain containing inositol 5-phosphatase SHIP2 is recruited to the epidermal growth factor (EGF) receptor and dephosphorylates phosphatidylinositol 3,4,5-trisphosphate in EGF-stimulated COS-7 cells. J Biol Chem 276:28348–28355PubMedGoogle Scholar
  113. Petry S, Baringhaus KH, Hoelder S, MüllerG (2002) Substituted and non-substituted benzooxathiazoles and compounds derived there from. Eur Patent Appl WO 2004/11722A1Google Scholar
  114. Podlecki DA, Frank BH, Olefsky JM (1984) In vitro characterization of human proinsulin. Diabetes 33:111–118PubMedGoogle Scholar
  115. Pope AJ, Haupts UM, Moore KJ (1999) Homogenous fluorescence readouts for miniaturized high-throughput screening: theory and practice. Drug Discov Today 4:350–362PubMedGoogle Scholar
  116. Ribel U, Hougaard P, Drejer K, Sørensen AR (1990) Equivalent in vivo biological activity of insulin analogs and human insulin despite different in vitro potencies. Diabetes 39:1033–1039PubMedGoogle Scholar
  117. Ricort JM, Tanti JF, Obberghen E, Le Marchand-Brustel Y (1997) Cross-talk between the platelet-derived growth factor and the insulin signaling pathways in 3T3-L1 adipocytes. J Biol Chem 272:19814–19818PubMedGoogle Scholar
  118. Robertson DA, Singh BM, Hale PJ, Jensen I, Nattrass M (1992) Metabolic effects of monomeric insulin analogs of different receptor affinity. Diabetes Med 9:240–246Google Scholar
  119. Saltiel AR (1996) Diverse signaling pathways in the cellular actions of insulin. Am J Physiol 270:375–385Google Scholar
  120. Sarbassov DD et al (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098–1101PubMedGoogle Scholar
  121. Sato M, Ozawa T, Inukai K, Asano T, Umezawa Y (2002) Fluorescent indicators for imaging protein phosphorylation in single living cells. Nat Biotechnol 20:287–294PubMedGoogle Scholar
  122. Schenk T, Appels NMGM, van Elswijk DA, Irth H, Tjaden UR, van der Greef J (2003) A generic assay for phosphate-consuming or –releasing enzymes coupled on-line to liquid chromatography for lead finding in natural products. Anal Biochem 316:118–126PubMedGoogle Scholar
  123. Schwartz GP, Burke GT, Katsoyannis PG (1987) A superactive insulin: [B10-aspartic acid]insulin(human). Proc Natl Acad Sci U S A 84:6408–6411PubMedCentralPubMedGoogle Scholar
  124. Scott JE, Carpenter JW (2003) A homogeneous assay of kinase activity that detects phosphopeptide using fluorescence polarization and zinc. Anal Biochem 316:82–91PubMedGoogle Scholar
  125. Sebbon B, Fynn GH (1973) Orthophosphate analysis by the Fiske-Subbarow method and interference by adenosine phosphates and pyrophosphate at variable acid pH. Anal Biochem 56:566–570Google Scholar
  126. Seethala R, Menzel R (1997) A homogeneous, fluorescence polarization assay for src-family tyrosine kinases. Anal Biochem 253:210–218PubMedGoogle Scholar
  127. Seethala R, Menzel R (1998) A fluorescence polarization competition immunoassay for tyrosine kinases. Anal Biochem 255:257–262PubMedGoogle Scholar
  128. Senn AM, Wolosiuk RA (2005) A high-throughput screening for phosphatases using specific substrates. Anal Biochem 339:150–156PubMedGoogle Scholar
  129. Serunian LA, Auger K, Cantley LC (1991) Identification and quantification of polyphosphoinositides produced in response to platelet-derived growth-factor stimulation. Methods Enzymol 198:78–87PubMedGoogle Scholar
  130. Shepherd PR (2005) Mechanisms regulating phosphoinositide 3-kinase signaling in insulin-sensitive tissues. Acta Physiol Scand 183:3–12PubMedGoogle Scholar
  131. Shepherd PR, Withers DJ, Siddle K (1998) Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J 333:471–490PubMedCentralPubMedGoogle Scholar
  132. Simeonov A, Bi X, Nikiforov TT (2002) Enzyme assays by fluorescence polarization in the presence of polyarginine: study for kinase, phosphatase, and protease reactions. Anal Biochem 304:193–199PubMedGoogle Scholar
  133. Sims CE, Allbritton NL (2003) Single-cell kinase assays: opening a window onto cell behavior. Curr Opin Biotechnol 14:23–28PubMedGoogle Scholar
  134. Stagljar I, Korostensky C, Johnsson N, te Heesen S (1998) A genetic system based on split-ubiquitin for the analysis of interactins between membrane proteins in vivo. Proc Natl Acad Sci U S A 95:5187–5192PubMedCentralPubMedGoogle Scholar
  135. Sun WC, Gee KR, Haughland RP (1998) Synthesis of novel fluorinated coumarins: excellent UV-light excitable fluorescent dyes. Bioorg Med Chem Lett 8:3107–3110PubMedGoogle Scholar
  136. Tashima Y (1975) Removal of protein interference in the Fiske-Subbarow method by sodium dodecyl sulfate. Anal Biochem 69:410–414PubMedGoogle Scholar
  137. Tavare JM, Denton RM (1988) Studies on the autophosphorylation of the insulin receptor from human placenta. Biochem J 252:607–615PubMedCentralPubMedGoogle Scholar
  138. Thaminy S, Auerbach D, Arnoldo A, Stagljar I (2003) Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system. Genome Res 13:1744–1753PubMedCentralPubMedGoogle Scholar
  139. Tonks NK (2003) Minireview: PTP1B: from the sidelines to the front lines! FEBS Lett 546:140–148PubMedGoogle Scholar
  140. Tornqvist HE, Avruch J (1988) Relationship of site-specific fi subunit tyrosine autophosphorylation to insulin activation of the insulin receptor protein kinase activity. J Biol Chem 263:4593–4601PubMedGoogle Scholar
  141. Trager JB, Martin GS (1997) The role of the Src homology-2 domain in the lethal effect of Src expression in the yeast Saccharomyces cerevisiae. Int J Biochem Cell Biol 29:635–648PubMedGoogle Scholar
  142. Tsien RY (1993) FRET for studying intracellular signalling. Trends Cell Biol 3:243–245Google Scholar
  143. Tsien RY (1998) The green fluorescent protein. Annu Rev Biochem 67:509–544PubMedGoogle Scholar
  144. Turek TC, Small EC, Bryant RW, Hill WAG (2001) Development and validation of a competitive AKT serine/threonine kinase fluorescence polarization assay using a product-specific anti-phospho-serine antibody. Anal Biochem 299:45–53PubMedGoogle Scholar
  145. Ungerer JP, Oosthuizen MH, Bissbort SH (1993) An enzymatic assay of inorganic phosphate in serum using nucleoside phosphorylase and xanthine oxidase. Clin Chim Acta 223:149–157PubMedGoogle Scholar
  146. Velloso LA, Folli F, Sun X-U, White MF, Saad MJA, Kahn CR (1996) Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci U S A 93:12490–12495PubMedCentralPubMedGoogle Scholar
  147. Verdier F, Chretien S, Billat C, Gisselbrecht S, Lacombe C, Mayeux P (1997) Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. J Biol Chem 272:26173–26178PubMedGoogle Scholar
  148. Vølund A, Brange J, Drejer K, Jensen I, Markussen J, Ribel U, Sørensen AR (1991) In vitro and in vivo potency of insulin analogs designed for clinical use. Diabetes Med 8:839–847Google Scholar
  149. Wada T, Sasaoka T, Funaki M, Hori H, Murakami M, Ishiki M, Haruta T, Asano T, Ogawa W, Ishihara H, Kobayashi M (2001) Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5′-phosphatase catalytic activity. Mol Cell Biol 21:1633–1646PubMedCentralPubMedGoogle Scholar
  150. Waddleton D, Ramachandran C, Wang Q (2002) Development of a time-resolved fluorescent assay for measuring tyrosine-phosphorylated proteins in cells. Anal Biochem 309:150–157PubMedGoogle Scholar
  151. Wahler D, Reymond J-L (2001) High-throughput screening for biocatalysts. Curr Opin Biotechnol 12:535–544PubMedGoogle Scholar
  152. Wang Q, Scheigetz J, Gilbert M, Snider JS, Ramachandran C (1999) Fluorescein monophosphates as fluorogenic substrates for protein tyrosine phosphatases. Biochim Biophys Acta 1431:14–23PubMedGoogle Scholar
  153. Watson RT, Pessin JE (2006) Bridging the GAP between insulin signaling and GLUT4 translocation. Trends Biochem Sci 31:215–222PubMedGoogle Scholar
  154. Webb MR (1992) A continuous spectrophotometric assay for inorganic phosphate and for measuring phosphate release kinetics in biological systems. Proc Natl Acad Sci U S A 89:4884–4887PubMedCentralPubMedGoogle Scholar
  155. Welsh GI et al (2005) Role of protein kinase B in insulin-regulated glucose uptake. Biochem Soc Trans 33:350–353Google Scholar
  156. Welte S, Tennagels N, Petry S (2003) Highly sensitive and continuous protein tyrosine phosphatase (PTPase) test using 6,8 difluoro-4-methyl-umbelliferylphosphate. Int Patent No WO03/056029 A2Google Scholar
  157. Welte S, Baringhaus K-H, Schmider W, Müller G, Petry S, Tennagels N (2005) 6,8-4-methylumbiliferyl phosphate: a fluorogenic substrate for protein tyrosine phosphatases. Anal Biochem 338:32–38PubMedGoogle Scholar
  158. White MF (1997) The insulin signalling system and the IRS proteins. Diabetologia 40:S2–S17PubMedGoogle Scholar
  159. White MF (1998) The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182:3–11Google Scholar
  160. White MF (2002) IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab 283:E413–E422PubMedGoogle Scholar
  161. Witt JJ, Roskoski R (1975) Rapid protein kinase assay using phosphocellulose-paper absorption. Anal Biochem 66:253–258PubMedGoogle Scholar
  162. Wouters FS (2001) Imaging biochemistry inside cells. Trends Cell Biol 11:203–211PubMedGoogle Scholar
  163. Wu JJ, Yarwood DR, Pham Q, Sills MA (2000) Identification of a high affinity anti-phosphoserine antibody for development of a homogeneous fluorescence polarization assay for protein kinase C. J Biol Mol Screen 5:23–30Google Scholar
  164. Wu P, Brand L (1994) Resonance energy transfer: methods and applications. Anal Biochem 218:1–13PubMedGoogle Scholar
  165. Xu Y (2002) Resonance energy transfer as an emerging technique for monitoring protein-protein interactions in vivo: BRET vs FRET. In: Van Dyke K (ed) Luminscence biotechnology: instruments and applications. CRC Press, New York, pp 529–538Google Scholar
  166. Xu Y, Piston DW, Johnson CH (1999) A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc Natl Acad Sci U S A 96:151–156PubMedCentralPubMedGoogle Scholar
  167. Xu J, Seet LF, Hanson B, Hong W (2001) The Phox homology (PX) domain, a new player in phosphoinositide signalling. Biochem J 360:513–530PubMedCentralPubMedGoogle Scholar
  168. Yamaguchi Y, Choi S, Sakamoto Y, Itakura K (1983) Purification of insulin receptor with full binding activity. J Biol Chem 258:5045–5049Google Scholar
  169. Yeh JI, Gulve EA, Rameh L, Birmbaum MJ (1997) The effects of wortmannin on rat skeletal muscle. Dissociation of signalling pathways for insulin- and contraction-activated hexose transport. J Biol Chem 270:2107–2111Google Scholar
  170. Yenush L, White MF (1997) The IRS-signalling system during insulin and cytokine action. Bioassays 19:491–500Google Scholar
  171. Zacharias DA (2000) Recent advances in technology for measuring and manipulating cell signals. Curr Opin Neurobiol 10:416–421PubMedGoogle Scholar
  172. Zeuzem S, Taylor R, Agius L, Albisser AM, Alberti KGMM (1984) Differential binding of sulphated insulin to adipocytes and hepatocytes. Diabetologia 27:184–188PubMedGoogle Scholar
  173. Zhang ZY (2003) Mechanistic studies on protein tyrosine phosphatases. Prog Nucleic Acid Res Mol Biol 73:171–220PubMedGoogle Scholar
  174. Zhang ZY, Dixon JE (1994) Protein tyrosine phosphatases: mechanisms of catalysis and substrate specificity. Adv Enzymol 68:1–36PubMedGoogle Scholar
  175. Zhang ZY, Maclean D, Thieme-Sefler AM, Roeske RW, Dixon JE (1993) A continuous spectrophotometric and fluorimetric assay for protein tyrosine phosphatase using phosphotyrosine-containing peptides. Anal Biochem 211:7–15PubMedGoogle Scholar
  176. Zhang B, Salituro G, Szalkowski D, Zhibua L, Zhang Y, Royo I, Vilella D, Diez MT, Pelaez F, Ruby C, Kendall RL, Mao X, Griffin P, Calaycay J, Zierath JR, Heck JV, Smith RG, Moller DE (1999) Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science 284:974–977PubMedGoogle Scholar

O-Linked Glycosylation (O-GlcNAc) of Insulin Signaling Components

  1. Arias EB, Kim J, Cartee GD (2004) Prolonged incubation in PUGNAc results in increased protein O-linked glycosylation and insulin resistance in rat skeletal muscle. Diabetes 53:921–930PubMedGoogle Scholar
  2. Birkelund S, Bini L, Pallini V, Sanchez-Campillo, Liberatori S, Clausen JD, Ostergaard S, Holm A, Christiansen G (1997) Characterization of Chlamydia trachomatis 12-induced tyrosine-phosphorylated HeLa cell proteins by two-dimensional gel electrophoresis. Electrophoresis 18:563–567PubMedGoogle Scholar
  3. Broschat KO, Gorka C, Kasten TP, Gulve EA, Kilpatrick B (2002) A radiometric assay for glutamine:fructose-6-phosphate amidotransferase. Anal Biochem 305:10–15PubMedGoogle Scholar
  4. Buse MG, Robinson KA, Marshall BA, Hresko RC, Mueckler MM (2002) Enhanced O-GlcNAc protein modification is associated with insulin resistance in GLUT1-overexpressing muscles. Am J Physiol Endocrinol Metab 283:E241–E250PubMedGoogle Scholar
  5. Chen H (2006) Cellular inflammatory responses: novel insights for obesity and insulin resistance. Pharmacol Res 53:469–477PubMedGoogle Scholar
  6. Comer FI, Vosseller K, Wells L, Accavitti MA, Hart GW (2001) Characterization of a mouse monoclonal antibody specific for O-linked N-acetylglucosamine. Anal Biochem 293:169–177PubMedGoogle Scholar
  7. Cooksey RC, McClain DA (2002) Transgenic mice overexpressing the rate-limiting enzyme for hexosamine synthesis in skeletal muscle or adipose tissue exhibit total body insulin resistance. Ann N Y Acad Sci 967:102–111PubMedGoogle Scholar
  8. Cordwell SJ, Nouwens AS, Verrills NM, Basseal DJ, Walsh BJ (2000) Subproteomics based upon protein cellular location and relative solubilities in conjunction with composite two-dimensional electrophoresis gels. Electrophoresis 21:1094–1103PubMedGoogle Scholar
  9. Dong DL, Hart GW (1994) Purification and characterization of an O-GlcNAc selective N-acetyl-beta-D-glucosaminidase from rat spleen cytosol. J Biol Chem 269:19321–19330PubMedGoogle Scholar
  10. Dunn MJ (1999) Methods Mol Biol 112:319–329PubMedGoogle Scholar
  11. Eldar-Finkelman H, Argast GM, Foord O, Fischer EH, Krebs EG (1996) Expression and characterization of glycogen synthase kinase-3 mutants and their effect on glycogen synthase activity in intact cells. Proc Natl Acad Sci U S A 93:10228–10233PubMedCentralPubMedGoogle Scholar
  12. Frick W, Bauer A, Bauer J, Wied S, Müller G (1998) Insulinmimetic signalling of synthetic phosphoinositolglycans in isolated rat adipocytes. Biochem J 336:163–181Google Scholar
  13. Fujita T, Furukawa S, Morita K, Ishihara T, Shiotani M, Matsushita Y, Matsuda M, Shimomura I (2005) Glucosamine induces lipid accumulation and adipogenic change in C2C12 myoblasts. Biochem Biophys Res Commun 328:369–374PubMedGoogle Scholar
  14. Gao Z, Hwang D, Bataille F, Lefebre M, York D, Quon MJ (2002) Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 277Google Scholar
  15. Gazdag AC, Wetter TJ, Davidson RT, Robinson KA, Buse MG, Yee AJ, Turcotte LP, Cartee GD (2000) Lower calorie intake enhances muscle insulin action and reduces hexosamine levels. Am J Physiol Regul Integr Comp Physiol 278:R504–R512PubMedGoogle Scholar
  16. Görg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R, Weiss W (2000) The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21:1037–1053PubMedGoogle Scholar
  17. Haltiwanger RS, Blomber MA, Hart GW (1992) Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-acetyl-glucosamine:polypeptide N-acetyltransferase. J Biol Chem 267:9005–9013PubMedGoogle Scholar
  18. Haltiwanger RS, Grove K, Philipsberg GA (1998) Modulation of O-linked N-acetylglucosamine levels on nuclear and cytoplasmic proteins in vivo using the peptide O-GlcNAc-beta-N-acetylglucosaminidase inhibitor O-(2-acet-amido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate. J Biol Chem 273:3611–3617PubMedGoogle Scholar
  19. Han D-H, Chen MM, Holloszy JO (2003) Glucosamine and glucose induce insulin resistance by different mechanisms in rta skeletal muscle. Am J Physiol Endocrinol Metab 285:E1267–E1272PubMedGoogle Scholar
  20. Hebert LF, Daniels MC, Zhou JX, Crook ED, Turner RL, Simmons ST, Neidigh JL, Zhu JS, Baron AD, McClain DA (1996) Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin Invest 98:930–936PubMedCentralPubMedGoogle Scholar
  21. Herbert B (1999) Advances in protein solubilisation for two-dimensional electrophoresis. Electrophoresis 20:660–663PubMedGoogle Scholar
  22. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Usyal KT, Maeda K (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336PubMedGoogle Scholar
  23. Johnsson B, Löfas S, Lindqvist G (1991) Immobilization of proteins to a carboxymethyldextran modified gold surface for biospecific interaction analysis in surface plasmon resonance. Anal Biochem 198:268–277PubMedGoogle Scholar
  24. Jönsson U, Fägerstam L, Johnsson B, Karlsson R, Lundh K, Löfas S, Persson B, Roos H, Rönnberg I (1991) Real-time biospecific interaction analysis using surface plasmon resonance and a sensor chip technology. Biotechniques 11:620–627PubMedGoogle Scholar
  25. Karam JH (1996) Reversible insulin resistance in non-insulin-dependent diabetes mellitus. Horm Metab Res 28:440–444PubMedGoogle Scholar
  26. Karlsson R, Stählberg R (1995) Surface plasmon resonance detection and multi-spot sensing for direct monitoring of interactions involving low molecular weight analytes and for determination of low affinities. Anal Biochem 228:274–280PubMedGoogle Scholar
  27. Kaufmann H, Bailey JE, Fussenegger M (2001) Use of antibodies for detection of phosphorylated proteins separated by two-dimensional gel electrophoresis. Proteomics 1:194–199PubMedGoogle Scholar
  28. Kreppel LK, Hart GW (1999) Regulation of a cytosolic and nuclear O-GlcNAc transferase: role of the tetratricopeptide repeats. J Biol Chem 274:32015–32022PubMedGoogle Scholar
  29. Kruszynska YT, Olefsky JM (1996) Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus. J Invest Med 44:413–428Google Scholar
  30. Löfas S (1995) Dextran modified self-assembled monolayer surfaces for use in biointeraction analysis with surface plasmon resonance. Pure Appl Chem 67:829–834Google Scholar
  31. Löfas S, Johnsson B, Edström A, Hansson A, Lindquist G, Müller Hillgren R-M, Stigh L (1995) Methods for site controlled coupling to carbosymethyldextran surfaces in surface plasmon resonance sensors. Biosens Bioelectron 10:9–10Google Scholar
  32. Malmqvist M, Karlsson R (1997) Biomolecular interaction analysis: affinity biosensor technologies for functional analysis of proteins. Curr Opin Chem Biol 1:378–383PubMedGoogle Scholar
  33. Marshall S (2002) The hexosamine signaling pathway: a new road to drug discovery. Curr Opin Endocrinol Diab 9:160–167Google Scholar
  34. Marshall S, Rumberger I (2000) The hexosamine signaling pathway: role in glucose sensing and integration of cellular metabolism. In: Walker M, Butler P, Rizza RA (eds) The diabetes annual/13. Elsevier, New York, pp 97–112Google Scholar
  35. Marshall S, Bacote V, Traxinger RR (1991a) Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system: role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266:4706–4712PubMedGoogle Scholar
  36. Marshall S, Garvey WT, Traxinger RR (1991b) New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids. FASEB J 5:3031–3036PubMedGoogle Scholar
  37. Marshall S, Nadeau O, Yamasaki K (2004) Dynamic actions of glucose and glucosamine on hexosamine biosynthesis in isolated adipocytes: differential effects on glucosamine 6-phosphate, UDP-N-acetylglucosamine, and ATP levels. J Biol Chem 279:35313–35319PubMedGoogle Scholar
  38. Marshall S, Nadeau O, Yamasaki K (2005a) Glucosamine-induced activation of glycogen biosynthesis in isolated adipocytes: evidence for a rapid allosteric control mechanism with the hexosamine biosynthesis pathway. J Biol Chem, in pressGoogle Scholar
  39. Marshall S, Yamasaki K, Okuyama R (2005b) Glucosamine induces rapid desensitization of glucose transport in isolated adipocytes by increasing GlcN-6-P levels. Biochem Biophys Res Commun 329:1155–1161PubMedGoogle Scholar
  40. McClain DA, Lubas WA, Cooksey RC, Hazel M, Parker GJ, Love DC, Hanover JA (2002) Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia. Proc Natl Acad Sci U S A 99:10695–10699PubMedCentralPubMedGoogle Scholar
  41. Molloy MP, Herbert BR, Williams KL, Gooley AA (1999) Extraction of Escherichia coli proteins with organic solvents prior to two-dimensional electrophoresis. Electrophoresis 20:701–704PubMedGoogle Scholar
  42. Mooney RA, Senn J, Cameron S, Inamdar N, Boivin LM, Shang Y (2001) Suppressors of cytokine signaling-1 and –6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance. J Biol Chem 276:25889–258993PubMedGoogle Scholar
  43. Müller G, Wied S, Frick W (2000a) Cross talk of pp125FAK and pp59Lyn non-receptor tyrosine kinases to insulinmimetic signaling in adipocytes. Mol Cell Biol 20:4708–4723PubMedCentralPubMedGoogle Scholar
  44. Myers MG, Sun X-J, White MF (1994) The IRS-1 signaling system. Trends Biochem Sci 19:289–293PubMedGoogle Scholar
  45. Nordin H, Jungnelius M, Karlsson R, Karlsson OP (2005) Kinetic studies of small molecule interactions with protein kinases using biosensor technology. Anal Biochem 340:359–368PubMedGoogle Scholar
  46. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021PubMedCentralPubMedGoogle Scholar
  47. Pickering AK (2004) Cytokine response to infection with Bacillus anthracis spores. Infect Immun 72:6382–6389PubMedCentralPubMedGoogle Scholar
  48. Rabilloud T, Adessi C, Giraudel A, Lunardi J (1997) Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21:1094–1103Google Scholar
  49. Robinson KA, Weinstein ML, Lindenmayer GE, Buse MG (1995) Effects of diabetes and hyperglycemia on the hexosamine synthesis pathway in rat muscle and liver. Diabetes 44:1438–1446PubMedGoogle Scholar
  50. Roquemore EP, Chou T, Hart GW (1994) Detection of O-linked n-acetylglucosamine (O-GlcNAc) on cytoplasmic and nuclear proteins. Methods Enzymol 230:443–460PubMedGoogle Scholar
  51. Rossetti L (1996) In: LeRoith D, Taylor SI, Olefsky JM (eds) Diabetes mellitus. Lippincott-Raven, Philadelphia, pp 544–553Google Scholar
  52. Rossetti L, Giaccari A, DeFronzo RA (1990) Glucose toxicity. Diabetes Care 13:610–630PubMedGoogle Scholar
  53. Rossetti L, Hawkins M, Chen W, Gindi J, Barzilai N (1995) In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 96:132–140PubMedCentralPubMedGoogle Scholar
  54. Sjölander S, Urbaniczky C (1991) Integrated fluid handling system for biomolecular interaction analysis. Anal Chem 63:2338–2345PubMedGoogle Scholar
  55. Steppan CM, Wang J, Whiteman EL, Birnbaum MJ, Lazar MA (2005) Activation of SOCS-3 by resistin. Mol Cell Biol 25:1569–1575PubMedCentralPubMedGoogle Scholar
  56. Szodoray P (2004) Circulating cytokines in primary Sjogrens syndrome determined by a multiplex cytokine system. Scan J Pharmacol 59:592–599Google Scholar
  57. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76:4350–4354PubMedCentralPubMedGoogle Scholar
  58. Ueki K, Kondo T, Kahn CR (2004) Suppressor of cytokine signaling 1 tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol 24:5434–5446PubMedCentralPubMedGoogle Scholar
  59. Vosseller K, Wells L, Hart GW (2001) Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics. Biochimie 83:575–581PubMedGoogle Scholar
  60. Vosseller K, Wells L, Lane MD, Hart GW (2002) Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A 99:5313–5318PubMedCentralPubMedGoogle Scholar
  61. Wang QM, Fiol CJ, DePaoli-Roach AA, Roach PJ (1994) Glycogen synthase kinase-3β is a dual specificity kinase differentially regulated by tyrosine and serine/threonine phosphorylation. J Biol Chem 269:14566–14574PubMedGoogle Scholar
  62. Wells L, Vosseller K, Hart GW (2001) Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science 291:2376–2378PubMedGoogle Scholar
  63. White MF (1998) The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182:3–11Google Scholar
  64. White MF (2003) Insulin signaling in health and disease. Science 302:1710–1711PubMedGoogle Scholar
  65. Yki-Järvinen H (1992) Glucose toxicity. Endocr Rev 13:415–431PubMedGoogle Scholar
  66. Yki-Järvinen, Vogt C, Iozzo P, Pipek R, Daniels MC, Virkamäki A, Mäkimattila S, Mandarino L, DeFronzo RA, McClain D, Gottschalk WK (1997) UDP-N-acetylglucosamine transferase and glutamine:fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia 40:76–81PubMedGoogle Scholar
  67. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y (2002) Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277:50230–50236PubMedGoogle Scholar
  68. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673–1677PubMedGoogle Scholar
  69. Zhou J, Neidigh JL, Espinosa R, LeBeau MM, McClain DA (1995) Human glutamine:fructose-6-phosphate amidotransferase: characterization of mRNA and chromosomal assignment to 2p13. Hum Genet 96:99–101PubMedGoogle Scholar

Lipid Raft- and Caveolae-Based Assays in Insulin and Insulin-Like Signal Transduction

  1. Abedinpour P, Jergil B (2003) Isolation of a caveolae-enriched fraction from rat lung by affinity partitioning and sucrose gradient centrifugation. Anal Biochem 313:1–8PubMedGoogle Scholar
  2. Anderson RGW (1993a) Caveolae: where incoming and outgoing messengers meet. Proc Natl Acad Sci U S A 90:10909–10913PubMedCentralPubMedGoogle Scholar
  3. Anderson RGW (1993b) Plasmalemmal caveolae and GPI-anchored membrane proteins. Curr Opin Cell Biol 5:647–652PubMedGoogle Scholar
  4. Anderson RGW (1998) The caveolae membrane system. Annu Rev Biochem 67:199–225PubMedGoogle Scholar
  5. Anderson RGW, Jacobson K (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296:1821–1825PubMedGoogle Scholar
  6. Avruch J, Wallach DF (1971) Preparation and properties of plasma membrane and endoplasmic reticulum fragments from isolated rat cells. Biochim Biophys Acta 233:334–347PubMedGoogle Scholar
  7. Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR (2000) CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature 407:202–207PubMedGoogle Scholar
  8. Baumann CA, Brady MJ, Saltiel AR (2001) Activation of glycogen synthase by insulin in 3T3-L1 adipocytes involves c-Cbl-associating protein (CAP)-dependent and CAP-independent signaling pathways. J Biol Chem 276:6065–6068PubMedGoogle Scholar
  9. Bickel PE (2002) Lipid rafts and insulin signaling. Am J Physiol Endocrinol Metab 282:E1–E10PubMedGoogle Scholar
  10. Brown DA, London E (1997) Breakthroughs and views. Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes ? Biochem Biophys Res Commun 240:1–7PubMedGoogle Scholar
  11. Brown DA, London E (1998) Structure and origin of ordered lipid domains in biological membranes. J Membr Biol 164:103–114PubMedGoogle Scholar
  12. Brown DA, Rose JK (1992) Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68:533–544PubMedGoogle Scholar
  13. Capozza F, Combs TP, Cohen AW, Cho Y-R, Park S-Y, Scherer PE, Kim JK, Lisanti MP (2005) Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle. Am J Physiol Cell Physiol 288:C1317–C1331PubMedGoogle Scholar
  14. Chang W-J, Ying Y, Rothberg KG, Hooper NM, Turner AJ, Gambliel HA, Gunzberg JD, Munmby SM, Gilamn AG, Anderson RGW (1994) Purification and characterization of smooth muscle cell caveolae. J Cell Biol 126:127–138PubMedGoogle Scholar
  15. Chiang SH, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL, Macara IG, Pessin JE, Saltiel AR (2001) Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410:944–948PubMedGoogle Scholar
  16. Cohen AW, Razani B, Schubert W, Williams TM, Wang XB, Iyengar P, Brasaemle DL, Scherer PE, Lisanti MP (2004) Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53:1261–1270PubMedGoogle Scholar
  17. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (1997a) Identification of peptide and protein ligands for the caveolin scaffolding domain. J Biol Chem 272:6525–6533PubMedGoogle Scholar
  18. Couet J, Sargiacomo M, Lisanti MP (1997b) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272:30429–30438PubMedGoogle Scholar
  19. Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC (2001) Loss of caveolae, vascular dysfunction and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293:2449–2452PubMedGoogle Scholar
  20. Edidin M (2003) The state of lipid rafts: from model membranes to cells. Annu Rev Biophys Biomol Struct 32:257–283PubMedGoogle Scholar
  21. Ekblad L, Jergil B (2001) Localization of phosphatidylinositol 4-kinase isoenzymes in rat liver plasma membrane domains. Biochim Biophys Acta 1531:209–221PubMedGoogle Scholar
  22. Fan JY, Carpentier JL, van Obberghen E, Grunfeld C, Gordon P, Orci L (1983) Morphological changes of the 3T3-L1 fibroblast plasma membrane upon differentiation to the adipocyte form. J Cell Sci 61:219–230PubMedGoogle Scholar
  23. Fujimoto T, Kogo H, Ishiguro K, Tauchi K, Nomura R (2001) Caveolin-2 is targeted to lipid droplets, a new “membrane domain” in the cell. J Cell Biol 152:1079–1085Google Scholar
  24. Glenney JR (1992) The sequence of human caveolin reveals identity with VIP 21, a component of transport vesicles. FEBS Lett 314:45–48PubMedGoogle Scholar
  25. Gustavsson J, Parpal S, Stralfors P (1996) Insulin-stimulated glucose uptake involves the transition of glucose transporters to a caveolae-rich fraction within the plasma membrane. Implications for Type II diabetes. Mol Med 2:367–372PubMedCentralPubMedGoogle Scholar
  26. Gustavsson J, Parpal S, Karsson M, Ramsing C, Thorn H, Borg M, Lindroth M, Peterson KH, Magnusson KE, Stralfors P (1999) Localization of the insulin receptor in caveolae of adipocyte plasma membrane. FASEB J 13:1961–1971PubMedGoogle Scholar
  27. Harder TP, Scheiffele P, Verkade P, Simons K (1998) Lipid domain structure of the plasma membrane revealed by patching of membrane components. J Cell Biol 141:929–942PubMedCentralPubMedGoogle Scholar
  28. Ishikawa Y, Otsu K, Oshikawa J (2005) Caveolin, different roles for insulin signal. Cell Signal 17:1175–1182PubMedGoogle Scholar
  29. Jones DR, Varela-Nieto I (1999) Diabetes and the role of inositol-containing lipids in insulin signaling. Mol Med 5:505–514PubMedCentralPubMedGoogle Scholar
  30. Ju H, Zou R, Venema VJ, Venema RC (1997) Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity. J Biol Chem 272:18522–18525PubMedGoogle Scholar
  31. Kandror KV, Stephens JM, Pilch PF (1995) Expression and compartmentalization of caveolin in adipose cells: coordinate regulation with and structural segregation from GLUT4. J Cell Biol 129:999–1006PubMedGoogle Scholar
  32. Kobzik T, Smith W, Kelly RA, Michel T (1996) Endothelial nitric oxide synthase targeting to caveolae. J Biol Chem 271:22810–22814PubMedGoogle Scholar
  33. Kurzchalia TV, Dupree P, Monier S (1994) VIP-21 Caveolin, a protein of the trans-Golgi network and caveolae. FEBS Lett 346:88–91PubMedGoogle Scholar
  34. Langtry HD, Balfour JA (1998) Glimepiride – a review of its pharmacological and clinical efficacy in the management of type 2 diabetes mellitus. Drugs 55:563–584PubMedGoogle Scholar
  35. Lisanti MP, Scherer PE, Tang ZL, Sargiacomo M (1994) Caveolae, caveolin and caveolin-rich membrane domains: a signaling hypothesis. Trends Cell Biol 4:231–235PubMedGoogle Scholar
  36. Macdonald JL, Pike LJ (2005) A simplified method for the preparation of detergent-free lipid rafts. J Lipid Res 46:1061–1067Google Scholar
  37. Mastick CC, Brady MJ, Saltiel AR (1995) Insulin stimulates the tyrosine phosphorylation of caveolin. J Cell Biol 129:1523–1531PubMedGoogle Scholar
  38. Mastick CC, Brady MJ, Printen JA, Ribbon V, Saltiel AR (1998) Spatial determinants of specificity of insulin action. Mol Cell Biochem 182:65–71PubMedGoogle Scholar
  39. Mayor S, Maxfield FR (1995) Insolubility and redistribution of GPI-anchored proteins at the cell surface after detergent treatment. Mol Biol Cell 6:929–944PubMedCentralPubMedGoogle Scholar
  40. Meshulam T, Simard JR, Wharton J, Hamilton JA, Pilch PF (2006) Role of caveolin-1 and cholesterol in transmembrane fatty acid movement. Biochemistry 45:2882–2893PubMedGoogle Scholar
  41. Mineo C, Ying Y-S, Chapline C, Jaken S, Anderson RGW (1998) Targeting of protein kinase C alpha to caveolae. J Cell Biol 141:601–610PubMedCentralPubMedGoogle Scholar
  42. Moffett S, Brown DA, Linder ME (2000) Lipid-dependent targeting of G proteins into rafts. J Biol Chem 275:2191–2198PubMedGoogle Scholar
  43. Müller G (2000b) The molecular mechanism of the insulinmimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl. Mol Med 6:907–933PubMedCentralPubMedGoogle Scholar
  44. Müller G (2002a) Dynamics of plasma membrane microdomains and cross-talk to the insulin signalling cascade (Invited Review). FEBS Lett 531:81–87PubMedGoogle Scholar
  45. Müller G, Frick W (1999a) Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin. CMLS, Cell Mol Life Sci 56:945–970PubMedGoogle Scholar
  46. Müller G, Welte S (2002a) Lipid raft domains are the targets for the insulin-independent blood glucose-decreasing activity of the sulfonylurea glimepiride. Recent Res Dev Endocrinol 3:401–423Google Scholar
  47. Müller G, Wied S, Frick W (2000b) Cross talk of pp125FAK and pp59Lyn non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes. Mol Cell Biol 20:4708–4723PubMedCentralPubMedGoogle Scholar
  48. Müller G, Jung C, Wied S, Welte S, Frick W (2001a) Insulin-mimetic signaling by the sulfonylurea glimepiride and phosphoinositolglycans involves distinct mechanisms for redistribution of lipid raft components. Biochemistry 40:14603–14620PubMedGoogle Scholar
  49. Müller G, Jung C, Wied S, Welte S, Jordan H, Frick W (2001b) Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes. Mol Cell Biol 21:4553–4567PubMedCentralPubMedGoogle Scholar
  50. Müller G, Hanekop N, Kramer W, Bandlow W, Frick W (2002a) Interaction of phosphoinositolglycan(-peptides) with plasma membrane lipid rafts of rat adipocytes. Arch Biochem Biophys 408:17–32PubMedGoogle Scholar
  51. Müller G, Hanekop N, Wied S, Frick W (2002b) Cholesterol depletion blocks redistribution of lipid raft components and insulin-mimetic signaling by glimepiride and phosphoinositolglycans in rat adipocytes. Mol Med 8:120–136PubMedCentralPubMedGoogle Scholar
  52. Müller G, Jung C, Frick W, Bandlow W, Kramer W (2002c) Interaction of phosphoinositolglycan(-peptides) with plasma membrane lipid rafts triggers insulin-mimetic signaling in rat adipocytes. Arch Biochem Biophys 408:7–16PubMedGoogle Scholar
  53. Müller G, Schulz A, Wied S, Frick W (2005b) Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes. Biochem Pharmacol 69:761–780PubMedGoogle Scholar
  54. Nystrom FH, Chen H, Cong LN, Li Y, Quon MJ (1999) Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells. Mol Endocrinol 13:2013–2024PubMedGoogle Scholar
  55. Oh P, Schnitzer JE (1999) Immunoisolation of caveolae with high affinity antibody binding to the oligomeric caveolin cage. Toward understanding the basis of purification. J Biol Chem 274:23144–23154PubMedGoogle Scholar
  56. Okamoto T, Schlegel A, Scherer PE, Lisanti MP (1998) Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 273:5419–5422PubMedGoogle Scholar
  57. Oshikawa J, Otsu K, Toya Y, Tsunematsu T, Hankins R, Kawabe J-I, Minamisawa S, Umemura S, Hagiwara Y, Ishikawa Y (2004) Insulin resistance in skeletal muscles of caveolin-3 null mice. Proc Natl Acad Sci U S A 101:12670–12675PubMedCentralPubMedGoogle Scholar
  58. Ostermeyer AG, Paci JM, Zeng Y, Lublin DM, Munro S, Brown DA (2001) Accumulation of caveolin in the endoplasmic reticulum redirects the protein to lipid storage droplets. J Cell Biol 152:1071–1078Google Scholar
  59. Parton RG (1996) Caveolae and caveolins. Curr Opin Cell Biol 8:542–548PubMedGoogle Scholar
  60. Persson A, Jergil B (1992) Purification of plasma membranes by aqueous two-phase affinity partitioning. Anal Biochem 204:131–136PubMedGoogle Scholar
  61. Persson A, Johansson B, Olsson H, Jergil B (1991) Purification of rat liver plasma membranes by wheat-germ-agglutinin partitioning. Biochem J 237:173–177Google Scholar
  62. Pol A, Luetterforst R, Lindsay M, Heino S, Ikonen E, Parton RG (2001) A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. J Cell Biol 152:1057–1070Google Scholar
  63. Pohl J, Ring A, Stremmel W (2002) Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a novel pathway. J Lipid Res 43:1390–1399PubMedGoogle Scholar
  64. Pohl J, Ring A, Korkmaz Ü, Ehehalt R, Stremmel W (2005) FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma membrane rafts. Mol Biol Cell 16:24–31PubMedCentralPubMedGoogle Scholar
  65. Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG (2001) Caveolin-1 null mice are viabele, but show evidence for hyper-proliferative and vascular abnormalities. J Biol Chem 276:38121–38138PubMedGoogle Scholar
  66. Razani B, Combs TP, Wang XB, Frank PG, Park DS, Russel RG, Li M, Tang B, Jelicks LA, Scherer PE, Lisanti MP (2002a) Caveolin-1 deficient mice are lean, resistant to diet-induced obesity and show hypertriglyceridemia with adipocyte abnormalities. J Biol Chem 277:8635–8647PubMedGoogle Scholar
  67. Razani B, Woodman SE, Lisanti MP (2002b) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–467PubMedGoogle Scholar
  68. Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel RA (1998) A novel, multifunctional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes. Mol Cell Biol 18:872–879PubMedCentralPubMedGoogle Scholar
  69. Rietveld A, Simons K (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376:467–479PubMedGoogle Scholar
  70. Rothberg KG, Henser JE, Donzell WC, Ying Y-S, Glenney JR, Anderson RGW (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682PubMedGoogle Scholar
  71. Sargiacomo M, Sudol M, Tang Z, Lisanti MP (1993) Signal transducing molecules and glycosyl-phosphatidylinositollinked proteins from a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 122:789–807PubMedGoogle Scholar
  72. Scherer PE, Lisanti MP, Baldini G, Sargiocomo M, Mastick CC, Lodish HF (1994) Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles. J Cell Biol 127:1233–1243PubMedGoogle Scholar
  73. Schlegel A, Volonte D, Engelman JA, Galbiati F, Mehta P, Zhang X-L (1998) Crowded little caves: structure and function of caveolae. Cell Signal 10:457–463PubMedGoogle Scholar
  74. Schnitzer JE, McIntosh DP, Dvorak AM, Liu J, Oh P (1995a) Separation of caveolae from associated microdomains of GPI-anchored proteins. Science 269:1435–1439PubMedGoogle Scholar
  75. Schnitzer JE, Oh P, Jaconson BS, Dvorak AM (1995b) Caveolae from luminal plasmalemma of rat lung endothelium: microdomains enriched in caveolin, Ca2+-ATPase, and inositol trisphosphate receptor. Proc Natl Acad Sci U S A 92:1759–1763PubMedCentralPubMedGoogle Scholar
  76. Shaul PW, Anderson RG (1998) Role of plasmalemmal caveolae in signal transduction. Am J Physiol Lung Cell Mol Physiol 275:L843–L851Google Scholar
  77. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572PubMedGoogle Scholar
  78. Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39PubMedGoogle Scholar
  79. Smart EJ, Ying Y, Mineo C, Anderson RGW (1995) A detergent-free method for purifying caveolae membrane from tissue culture cells. Proc Natl Acad Sci U S A 92:10104–10108PubMedCentralPubMedGoogle Scholar
  80. Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP (1999) Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 19:7289–7304PubMedCentralPubMedGoogle Scholar
  81. Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP (1996) Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. J Biol Chem 271:9690–9697PubMedGoogle Scholar
  82. Stan R-V, Roberts WG, Predescu K, Ihida L, Saucan L, Ghitescu L, Palade GE (1997) Immunoisolation and partial characterization of endothelial plasmalemmal vesicles (caveolae). Mol Biol Cell 8:595–605PubMedCentralPubMedGoogle Scholar
  83. Wasner HK, Müller G, Eckel J (2003) Direct comparison of inositol phosphoglycan with prostaglandylinositol cyclic phosphate, two potential mediators of insulin action. Exp Clin Endocrinol Diabetes 111:358–363PubMedGoogle Scholar

Glycosyl-Phosphatidylinositol-Specific Phospholipase (GPI-PL) and Insulin-Like Signaling

  1. Bähr M, von Holtey M, Müller G, Eckel J (1995) Direct stimulation of myocardial glucose transport and glucose transporter-1 (GLUT1) and GLUT4 protein expression by the sulfonylurea glimepiride. Endocrinology 136:2547–2553Google Scholar
  2. Bordier C (1981) Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem 256:1604–1607PubMedGoogle Scholar
  3. Chan BL, Lisanti MP, Rodriguez-Boulan E, Saltiel AR (1988) Insulin-stimulated release of lipoprotein lipase by metabolism of its phosphatidinylinositol anchor. Science 241:1670–1672PubMedGoogle Scholar
  4. Cross GAM (1990) Glycolipid anchoring of plasma membrane proteins. Annu Rev Cell Biol 6:1–39PubMedGoogle Scholar
  5. Farese RV (1990) Lipid-derived mediators in insulin action. Proc Soc Exp Biol Med 195:312–324PubMedGoogle Scholar
  6. Ferguson MAJ (1991) Lipid anchors on membrane proteins. Curr Opin Struct Biol 1:522–529Google Scholar
  7. Fonteles MC, Huang LC, Larner J (1996) Infusion of pH 2.0 D-chiro-inositol glycan insulin putative mediator normalizes plasma glucose in streptozotocin diabetic rats at a dose equivalent to insulin without inducing hypoglycemia. Diabetologia 39:731–734PubMedGoogle Scholar
  8. Gaulton GN, Pratt JC (1994) Glycosylated phosphatidylinositol molecules as second messengers. Semin Immunol 6:97–104PubMedGoogle Scholar
  9. Jones DR, Varela-Nieto I (1998) The role of glycosyl-phosphatidylinositol in signal transduction. Int J Biochem Cell Biol 30:313–326PubMedGoogle Scholar
  10. Larner J (1987) Banting lecture: insulin signaling mechanisms. Lessons from the old testament of glycogen metabolism and the new testament of molecular biology. Diabetes 37:262–275Google Scholar
  11. Lawrence JC, Hiken JF, Inkster M, Scott CW, Mumby MC (1986) Insulin stimulates the generation of an adipocyte phosphoprotein that is isolated with a monoclonal antibody against the regulatory subunit of bovine heart cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 83:3649–3653PubMedCentralPubMedGoogle Scholar
  12. Lazar DF, Knez JJ, Medof ME, Cuatrecasas P, Saltiel AR (1994) Stimulation of glycogen synthesis by insulin in human erythroleukemia cells requires the synthesis of glycosyl-phosphatidylinositol. Proc Natl Acad Sci U S A 91:9665–9669PubMedCentralPubMedGoogle Scholar
  13. Lewis KA, Garigapati VR, Zhou C, Roberts MF (1993) Substrate requirements of bacterial phosphatidinylinositol-specific phospholipase C. Biochemistry 32:8836–8841PubMedGoogle Scholar
  14. Lisanti MP, Darnell JC, Chan BL, Rodriguez-Boulan E, Saltiel AR (1989) The distribution of glycosyl-phosphatidylinositol anchored proteins is differentially regulated by serum and insulin. Biochem Biophys Res Commun 164:824–832PubMedGoogle Scholar
  15. Low MG (1989) The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim Biophys Acta 988:427–454PubMedGoogle Scholar
  16. Low MG (1990) Degradation of glycosyl-phosphatidylinositol anchors by specific phospholipases. In: Turner AJ (ed) Molecular and cell biology of membrane proteins. Glycolipid anchors of cell-surface proteins. Ellis Horwood, New York, pp 35–63Google Scholar
  17. Low MG, Saltiel AR (1988) Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science 239:268–275PubMedGoogle Scholar
  18. Low MG, Stiernberg J, Waneck GL, Flavell RA, Kincade PW (1988) Cell-specific heterogeneity in sensitivity of phosphatidinylinositol-anchored membrane antigens to release by phospholipase C. J Immunol Methods 113:101–111PubMedGoogle Scholar
  19. Macdonald JL, Pike LJ (2005) A simplified method for the preparation of detergent-free lipid rafts. J Lipid Res 46:1061–1067Google Scholar
  20. Mato JM (1989) Insulin mediators revisited. Cell Signal 1:143–146PubMedGoogle Scholar
  21. Movahedi S, Hooper NM (1997) Insulin stimulates the release of the glycosyl phosphatidylinositol-anchored membrane dipeptidase from 3T3-L1 adipocytes through the action of a phospholipase C. Biochem J 326:531–537PubMedCentralPubMedGoogle Scholar
  22. Müller G (2000c) The molecular mechanism of the insulinmimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl. Mol Med 6:907–933PubMedCentralPubMedGoogle Scholar
  23. Müller G (2002b) Dynamics of plasma membrane microdomains and cross-talk to the insulin signalling cascade (Invited Review). FEBS Lett 531:81–87PubMedGoogle Scholar
  24. Müller G (2002c) Concepts and options for current insulin research and future anti-diabetic therapy. Recent Res Dev Endocrinol 3:199–218Google Scholar
  25. Müller G (2005) The mode of action of the antidiabetic drug glimepiride-beyond insulin secretion. Curr Med Chem Immune Metab Agents 5:499–518Google Scholar
  26. Müller G, Bandlow W (1991) A cAMP binding ectoprotein in the yeast Saccharomyces cerevisiae. Biochemistry 30:10181–10190PubMedGoogle Scholar
  27. Müller G, Frick W (1999b) Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin. CMLS, Cell Mol Life Sci 56:945–970PubMedGoogle Scholar
  28. Müller G, Welte S (2002b) Lipid raft domains are the targets for the insulin-independent blood glucose-decreasing activity of the sulfonylurea glimepiride. Recent Res Dev Endocrinol 3:401–423Google Scholar
  29. Müller G, Wied S (1993) The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro. Diabetes 42:1852–1867PubMedGoogle Scholar
  30. Müller G, Dearey EA, Punter J (1993) The sulfonylurea drug, glimepiride, stimulates release of glycosylphosphatidylinositol-anchored plasma membrane proteins from 3T3 adipocytes. Biochem J 289:509–521PubMedCentralPubMedGoogle Scholar
  31. Müller G, Dearey E-A, Korndörfer A, Bandlow W (1994b) Stimulation of a glycosyl phosphatidylinositol-specific phospholipase by insulin and the sulfonylurea, glimepiride, in rat adipocytes depends on increased glucose transport. J Cell Biol 126:1267–1276PubMedGoogle Scholar
  32. Müller G, Korndörfer A, Saar K, Karbe-Thönges B, Fasold H, Mullner S (1994c) 4′-amino-benzamido-taurocholic acid selectively solubilizes glycosyl-phosphatidylinositol-anchored membrane proteins and improves lipolytic cleavage of their membrane anchors by specific phospholipases. Arch Biochem Biophys 309:329–340PubMedGoogle Scholar
  33. Müller G, Wetekam E-A, Jung C, Bandlow W (1994d) Membrane association of lipoprotein lipase and a cAMP-binding ectoprotein in rat adipocytes. Biochemistry 33:12149–12159PubMedGoogle Scholar
  34. Müller G, Wied S, Wetekam EM, Crecelius A, Pünter J (1994e) Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulfonylureas glimiperide and glibenclamide, is correlated with modulations of the cAMP regulatory cycle. Biochem Pharmacol 48:985–996PubMedGoogle Scholar
  35. Müller G, Jung C, Wied S, Welte S, Frick W (2001c) Insulin-mimetic signaling by the sulfonylurea glimepiride and phosphoinositolglycans involves distinct mechanisms for redistribution of lipid raft components. Biochemistry 40:14603–14620PubMedGoogle Scholar
  36. Müller G, Jung C, Wied S, Welte S, Jordan H, Frick W (2001d) Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes. Mol Cell Biol 21:4553–4567PubMedCentralPubMedGoogle Scholar
  37. Müller G, Hanekop N, Wied S, Frick W (2002d) Cholesterol depletion blocks redistribution of lipid raft components and insulin-mimetic signaling by glimepiride and phosphoinositolglycans in rat adipocytes. Mol Med 8:120–136PubMedCentralPubMedGoogle Scholar
  38. Müller G, Schulz A, Wied S, Frick W (2005c) Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes. Biochem Pharmacol 69:761–780PubMedGoogle Scholar
  39. Nosjean O, Briolay A, Roux B (1997) Mammalian GPI proteins: sorting, membrane residence and functions. Biochim Biophys Acta 1331:153–186PubMedGoogle Scholar
  40. Pryde JG, Phillips JH (1986) Fractionation of membrane proteins by temperature-induced phase separation in Triton X-114. Biochem J 233:525–533PubMedCentralPubMedGoogle Scholar
  41. Romero G, Larner J (1993) Insulin mediators and the mechanism of insulin action. Adv Pharmacol 24:21–50PubMedGoogle Scholar
  42. Romero G, Luttrell L, Rogol A, Zeller K, Hewlett E, Larner J (1988) Phosphatidylinositol-glycan anchors of membrane proteins: potential precursors of insulin mediators. Science 240:509–512PubMedGoogle Scholar
  43. Romero GL, Gamez G, Huang LC, Lilley K, Luttrell L (1990) Antiinositolglycan antibodies selectively block some of the actions of insulin in intact BC3H1 cells. Proc Natl Acad Sci U S A 87:1476–1480PubMedCentralPubMedGoogle Scholar
  44. Saltiel AR, Fox JA, Sherline P, Cuatrecasas P (1986) Insulin stimulates the generation from hepatic plasma membranes of modulators derived from an inositol glycolipid. Science 233:967–972PubMedGoogle Scholar
  45. Saltiel AR, Osterman DG, Darnell JC, Sorbara-Cazan LR, Chan BL, Low MG, Cuatrecasas P (1988) The function of glycosyl phosphoinositides in hormone action. Philos Trans R Soc Lond B320:345–358Google Scholar
  46. Satiel AR (1990) Second messengers of insulin action. Trends Endocrinol Metab 1:158–163Google Scholar
  47. Shashkin PN, Shashkina EF, Fernqvist-Forbes E, Zhou Y-P, Grill V, Katz A (1997) Insulin mediators in man: effects of glucose and insulin resistance. Diabetologia 40:557–563PubMedGoogle Scholar
  48. Thomas JR, Dwek RA, Rademacher TW (1990) Structure, biosynthesis and function of gylcosylphosphatidinylinositols. Biochemistry 29:5413–5422PubMedGoogle Scholar
  49. Varela-Nieto I, Leon Y, Caro HN (1996) Cell signalling by inositol phosphoglycans from different species. Comp Biochem Physiol 115B:223–241Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Helmholtz MünchenMunichGermany

Personalised recommendations