Skip to main content
SpringerLink
Log in

Insulin Resistance and Inhibitors of Insulin Receptor Tyrosine Kinase

  • Chapter
Insulin Resistance

Part of the book series: Contemporary Endocrinology ((COE,volume 12))

  • 221 Accesses

Abstract

Noninsulin dependent diabetes mellitus (NIDDM or Type 2 diabetes mellitus) occurs in approximately 5% of the US population (1). The vast majority of these patients display resistance to the biological actions of insulin (2). Insulin resistance both precedes and contributes to the development of the diabetic state (3,4). In addition to Type 2 diabetes patients, insulin resistance occurs in most patients with impaired glucose tolerance and some individuals with normal glucose tolerance (1,4,5). In these people, normoglycemia is maintained by a compensatory hypersecretion of insulin. Progression to frank diabetes generally occurs when insulin secretion by the pancreatic β-cells is no longer sufficient to overcome the peripheral resistance to the hormone (1). There are both genetic and acquired factors which can produce insulin resistance, and thus predispose an individual to Type 2 diabetes (6). Obesity is the most common cause of acquired insulin resistance in Western Society. One-third to one-half of Americans are defined as overweight, and up to 80% of Type 2 diabetes patients are obese. Numerous studies have shown that insulin stimulated glucose disposal declines as a function of increasing obesity (Fig. 1) (7).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. King H, Rewers M, WHO Ad Hoc Diabetes Reporting Group. Global estimates for the prevelance of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care 1993; 16: 137–177.

    Article  Google Scholar 

  2. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  3. Martin BC, Warram JH, Krowlewski AS, Bergman RN, Soelder JS, Kahn CR. Role of glucose and insulin resistence in development of type II diabetes mellitus: results of a 25-year follow-up study. Lancet 1992; 340: 925–929.

    Article  PubMed  CAS  Google Scholar 

  4. Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C. Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies of Pima Indians. N Engl J Med 1988; 318: 1217–1225.

    Article  PubMed  CAS  Google Scholar 

  5. Hollenbeck C, Reaven G M. Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987; 64: 1169–1173.

    Article  PubMed  CAS  Google Scholar 

  6. Hamman RF. Genetic and environmental determinants of non-insulin-dependent-diabetes mellitus (NIDDM). Diabet Metabol Rev 1992; 8: 287–338.

    Article  CAS  Google Scholar 

  7. Bogardus C, Lillioja S, Mott DM, Hollenbeck C, Reaven G M. Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol 1985; 248: E286 - E291.

    PubMed  CAS  Google Scholar 

  8. Vaag A, Henriksen JE, Beck-Nielsen H. Decreased insulin activation of glycogen synthase in skeletal muscles in young non-obese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1992; 89: 782–788.

    Article  PubMed  CAS  Google Scholar 

  9. Lillioja S, Mott DM, Zawadzi KK, Young AA, Abbott WGH, Knowler WC, Bennett PH, Moll P, Bogardus C. In vivo insulin action is a familial characteristic in nondiabetic Pima Indians. Diabetes 1987; 36: 1329–1335.

    Article  PubMed  CAS  Google Scholar 

  10. Martin BC, Warram JH, Rosner B, Rich SS, Soeldner JS, Krolewski AS. Familial clustering of insulin sensitivity. Diabetes 1992; 41: 850–854.

    Article  PubMed  CAS  Google Scholar 

  11. Vaag A, Henriksen JE, Madsbad S, Holm, N, Beck-Neilsen H. Insulin secretion, insulin action, hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 95: 690–698.

    Article  PubMed  CAS  Google Scholar 

  12. Taylor, SI. Lessons from patients with mutations in the insulin-receptor gene. Diabetes 1992; 41: 1473.

    Article  PubMed  CAS  Google Scholar 

  13. Goldfine, ID. The insulin receptor: molecular biology and transmembrane signaling. Endocr Rev 1987; 8: 235.

    Article  PubMed  CAS  Google Scholar 

  14. Kahn CR, White MF. The insulin receptor and the molecular mechanism of insulin action. J Clin Invest 1988; 82: 1551.

    Google Scholar 

  15. Rosen OM, Herrera R, Olowe Y, Petruzelli LM, Cobb MH. Phosphorylation activates the insulin receptor tyrosine protein kinase. Proc Natl Acad Sci USA 1983; 80: 3237–3240.

    Article  PubMed  CAS  Google Scholar 

  16. Moran ME, Koch CA, Anderson D, Ellis C, England L, Martin GS, Pawson T. Src Homology region 2 domains direct protein-protein-interactions in signal transduction. Proc Natl Acad Sci USA 1990; 87: 8622–8626.

    Article  PubMed  CAS  Google Scholar 

  17. White MF. The IRS-1 signaling system. Curr Opin Genet Devel 1994; 4: 47–54.

    Article  CAS  Google Scholar 

  18. Okada,T, Kamano Y, Sakakibara T, Hazeki 0, Ui M. Essential role of phosphotidylinositol 3-kinase in insulin induced glucose transport and antilopolysis in rat adipocytes. J Biol Chem 1994; 269: 3568–3573.

    Google Scholar 

  19. Cheatham B, Vlahos CJ, Cheatam L, Wang L, Blenis J, Kahn CR. (1994) Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis and glucose transporter translocation. Mol Cell Biol 14: 4902–4911.

    Google Scholar 

  20. DeFronzo RA. The triumvirate: B-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 1988; 37: 667–687.

    PubMed  CAS  Google Scholar 

  21. Reaven GM. The Fourth Muskateer-from Alexandre Dumas to Claude Bernard. Diabetologia 1995; 38: 3–13.

    Article  PubMed  CAS  Google Scholar 

  22. Dohm GL, Tapscott EB, Pories WJ, Dabbs DJ, Flickinger EF, Meelheim D, Fushiki T, Atkinson SM, Elton CW, Dohm GL. An in vitro human muscle preparation suitable for metabolic studies: decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest 1988; 82: 486–494.

    Article  PubMed  CAS  Google Scholar 

  23. Youngren JF, Maddux BA, Sasson S, Sbraccia P, Tapscott EB, Swanson MS, Dohm GL, Goldfine ID. Skeletal muscle content of membrane glycoprotein PC-1 in obesity: relationship to muscle glucose transport. Diabetes 1996; 45: 1324–1328.

    Article  PubMed  CAS  Google Scholar 

  24. Olefsky JM, Garvey WT, Henry RR, Brillon D, Matthaei S, andFreidenberg GR. Cellular mechanisms of insulin resistance in non-insulin-dependent (type II) diabetes. Am J Med 1988; 85 (Suppl 5A): 86–105.

    Article  PubMed  CAS  Google Scholar 

  25. Garvey WT, Maianu L, Huecksteadt TP, Birnbaum MJ, Molina JM, Ciraldi TP. Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with noninsulin-dependent diabetes mellitus and obesity. J Clin Invest 1991; 87: 1072–1081.

    Article  PubMed  CAS  Google Scholar 

  26. Krentz AJ, Nattrass M. Insulin resistance: a multifacted metabolic syndrome. Insights gained using a low-dose insulin infusion technique. Diabetic Med 1996; 13: 30–39.

    Article  PubMed  CAS  Google Scholar 

  27. Campbell PJ, Carlson MC, Nourijahan, N. Fat metabolism in human obesity. Am J Physiol 1994; E600 - E605.

    Google Scholar 

  28. Rebrin K, Steil GM, Mittelman SD, Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest 1996; 38: 741–749.

    Article  Google Scholar 

  29. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbance of diabetes mellitus. Lancet 1963; 1: 785–789.

    Article  PubMed  CAS  Google Scholar 

  30. Garvey WT, Maianu L, Huecksteadt TP, Birnbaum MJ, Molina JM, Ciaraldi TP. Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with noninsulin-dependent diabetes mellitus and obesity. J Clin Invest 1991; 87: 1072–1081.

    Article  PubMed  CAS  Google Scholar 

  31. Pedersen O, Kahn CR, Flier JS, Kahn BB. High fat feeding causes insulin resistance and a marked decrease in the expression of glucose transporters (GLUT4) in fat cells of rats. Endocrinology 1991; 129: 771–777.

    Article  PubMed  CAS  Google Scholar 

  32. Sivitz WI, DeSautel SL, Kayano T, Bell GI, Pessin JE. Regulation of glucose transporter mRNA in insulin-deficient states. Nature 1989; 340: 72–74.

    Article  PubMed  CAS  Google Scholar 

  33. Rodnick KJ, Piper RC, Slot JW, James DE. Interaction of insulin and exercise on glucose transport in muscle. Diabetes Care 1992; 15: I679–1689.

    Article  Google Scholar 

  34. Youngren JF, Barnard RJ. Effects of acute and chronic exercise on skeletal muscle glucose transport in aged rats. J Appl Physiol 1995; 78 (5): 1750–1756.

    PubMed  CAS  Google Scholar 

  35. Pedersen O, Bak JF, Andersen PH, Lund S, Moller DE, Flier JS, Kahn BB. Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes 1990; 39: 865–870.

    Article  PubMed  CAS  Google Scholar 

  36. Goodyear LJ, Giorgino F, Sherman LA, Carey J, Smith RJ, Dohm GL. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest 1995; 95: 2195–2204.

    Article  PubMed  CAS  Google Scholar 

  37. Sommercorn J, Fields R, Raz I, Maeda R. Abnormal regulation of ribosomal protein S6 kinase by insulin in skeletal muscle of insulin resistant humans J Clin Invest 1993; 91: 509–513.

    CAS  Google Scholar 

  38. Boulware SD, Tamborlane WV, Rennert NJ, Gesundheit N, Sherwin RS. Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults. J. Clin. Invest 1994; 93: 1131–1139.

    Article  PubMed  CAS  Google Scholar 

  39. Eldar-Finkelman H, Krebs EG. Phospsorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc Natl Acad Sci USA 1997; 94: 9660–9664.

    Article  PubMed  CAS  Google Scholar 

  40. Hotamisiligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1 mediated inhibition of insulin receptor tyrosine kinase activity in TNFa and obesity-induced insulin resistance. Science 1996; 271: 665–668.

    Article  Google Scholar 

  41. Caro JF, Sinha MK, Raju SM, Ittoop O, Pories WJ, Flickinger EG, Meelheim D, Dohm GL. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. J Clin Invest 1987; 79: 1330–1337.

    Article  PubMed  CAS  Google Scholar 

  42. Nyomba BL, Ossowski VM, Bogardus C, Mott DM. Insulin-sensitive tyrosine kinase: relationship with in vivo insulin action in humans. Am J Physiol 1990; 258: E964 - E974.

    PubMed  CAS  Google Scholar 

  43. Grasso G, Frittitta L, Anello M, Russo P, Susti G, Trischitta V. Insulin receptor tyrosine kinase activity is altered in both muscle and adipose tissue from nonobese normoglycemic insulin resistant subjects. Diabetologia. 1995; 3 8: 5 5–61.

    Google Scholar 

  44. Handberg A, Vaag A, Vinten J, Beck-Nielsen H. Decreased tyrosine kinase activity in partially purified insulin receptors from muscle of young, nonobese first degree relatives patients with type 2 (non-insulindepedent) diabetes mellitus. Diabetologia. 1993; 36: 668–674.

    Article  PubMed  CAS  Google Scholar 

  45. Maegawa H, Shigeta Y, Egawa K, Kobayashi M. Impaired otophosphorylation of insulin receptors from abdominal skeletal muscles in non-obese subjects with NIDDM. Diabetes 1991; 40: 815–819.

    Article  PubMed  CAS  Google Scholar 

  46. Obermaier-Kusser B, White MF, Pongratz DE, Su Z, Ermal B, Muhlbacher C, Haring HU. A defective intramolecular autoactivation cascade may cause the reduced kinase activity of the skeletal muscle insulin receptor from patients with non-insulin-depedent diabetes mellitus. J Biol Chem 1989; 264: 9497–9504.

    PubMed  CAS  Google Scholar 

  47. Scheck SH, Barnard RJ, Lawani LO, Youngren JF, Martin DA, Singh R. Effects of NIDDM on glucose transport system in human skeletal muscle. Diabetes Res 1991; 16: 111–119.

    PubMed  CAS  Google Scholar 

  48. Arner P, Pollare T, Lithell H, Livingston JN. Defective insulin receptor tyrosine kinase in human skeletal muscle in obesity and Type 2. (non-insulin-dependent) diabetes mellitus. Diabetologia 1987; 30: 437–440.

    Article  PubMed  CAS  Google Scholar 

  49. Nolan JJ, Freidenberg G, Henry R, Reichart D, Olefsky JM. Role of human skeletal muscle insulin receptor kinase in the in vivo insulin resistance of noninsulin-dependent diabetes mellitus and obesity. J Clin Endocrinol Metab 1994; 78: 471–477.

    Article  PubMed  CAS  Google Scholar 

  50. Dunaif A, Xia J, Book, C-B, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle: a potential mechanism for insulin resistance in the Polycystic Ovary Syndrome. J Clin Invest 1995; 96: 801–810.

    Article  PubMed  CAS  Google Scholar 

  51. Takayama S, Kahn CR, Kubo K, Foley JE. Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin. J Clin Endocrinol Metab 1987; 66: 992–999.

    Article  Google Scholar 

  52. Klein HH, Vestergaard H, Koetzke G, Pedersen O. Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM. Diabetes 1995; 44: 1310–1317.

    Article  PubMed  CAS  Google Scholar 

  53. Freidenberg GR, Henry RR, Reichart DR, Olefsky JM. Decreased kinase activity of insulin receptors from adicocytes of non-insulin-dependent diabetic subjects. J Clin Invest 1987; 79: 240–250.

    Article  PubMed  CAS  Google Scholar 

  54. Frittitta L, Youngren JF, Vigneri R, Maddux BA, Trischitta V, Goldfine ID. PC-1 content in skeletal muscle of non-obese, non-diabetic subjects, relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity. Diabetologia 1996; 39: 1190–1195.

    Article  PubMed  CAS  Google Scholar 

  55. Frittitta L, Youngren JF, Sbraccia P, D’Adamo M, Boungiorno A, Vigneri R, Goldfine ID, Trischitta V. Increased adispose tissue PC-1 protein content, but not TNF-a gene expression, is associated to a reduction of both whole body insulin sensitivity and insulin receptor tyrosine kinase activity. Diabetologia 1997; 40: 282–289.

    Article  PubMed  CAS  Google Scholar 

  56. Youngren J.F, Goldfine ID, Pratley RE. Decreased muscle insulin receptor kinase correlates with insulin resistance in normoglycemic Pima Indians. Am J Physiol 1997; 273: E276 - E283.

    PubMed  CAS  Google Scholar 

  57. Moller DE, Chang, P-Y, Yaspelkis III BB, Flier JS, Walberg-Henriksson H, Ivy JL. Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, dyslipemia. Endocrinology 1996; 137: 2397–2405.

    Article  PubMed  CAS  Google Scholar 

  58. Bollag GE, Roth RA, Beaudoin J, Mochly-Rosen D, Koshland DEJ. Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein tyrosine kinase activity. Proc Natl Acad Sci USA 1986; 83: 5822–5824.

    Article  PubMed  CAS  Google Scholar 

  59. Kellerer M, Coghlan M, Capp E, Mühlhöfer A, Kroder G, Mosthaf L, Galante P, Siddle K, Häring HU. Mechanism of insulin receptor kinase inhibition in non-insulin-dependent diabetes mellitus patients: phosphorylation of serine 1327 or threonine 1348 is unaltered. J Clin Invest 1995; 96: 6–11.

    Article  PubMed  CAS  Google Scholar 

  60. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, relationship to liproprotein lipase. J Clin Invest 1995; 95: 2111–2119.

    Article  PubMed  CAS  Google Scholar 

  61. Hotamisiligil GS, Shargill, N.S, Spiegelman BM. Adipose expression of tumor necrosis factor-a: direct role in obesity-linked insulin resistance. Science 1993; 259: 87–91.

    Article  Google Scholar 

  62. Fofei, Hurel S, Newkirk J, Sopwith M, Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996; 45: 881–885.

    Article  Google Scholar 

  63. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-a function. Nature 1997; 389: 610–614.

    Article  PubMed  CAS  Google Scholar 

  64. Mosthaf L, Vogt B, Haring HU, Ullrich A. Altered expression of insulin receptor types A and B in the skeletal muscle of non-insulin-dependent diabetes mellitus patients. Proc Natl Acad Sci USA 1991; 88: 4728–4730.

    Article  PubMed  CAS  Google Scholar 

  65. Benecke H, Flier JS, Moller DE. Alternative spliced variants of the insulin receptor protein, expression in normal and diabetic human tissues. J Clin Invest 1992; 89: 2066–2070.

    Article  PubMed  CAS  Google Scholar 

  66. Hansen T, Bjorback C, Vestergaard H, Gronskov K, Bak JF, Pedersen O. Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993; 77: 1500–1505.

    Article  PubMed  CAS  Google Scholar 

  67. Sell SM, Reese D, Ossowski VM. Insulin-inducible changes in insulin receptor mRNA splice variants. J Biol Chem 1994; 269: 30769–30772.

    PubMed  CAS  Google Scholar 

  68. Kosaki A, Pillay TS, Xu L, Webster, NJ. The B soform of the insulin receptor signals more efficiently than the A isoform in Hep G2 cells. J Biol Chem 1995; 270: 20816–20823.

    Article  PubMed  CAS  Google Scholar 

  69. Sbraccia P, Goodman PA, Maddux BA, Chen Y-DI, Reaven GM, Goldfine ID. Production of an inhibitor of insulin receptor tyrosine kinase in fibroblasts from a patient with insulin resistance and NIDDM. Diabetes 1991; 40: 295–299.

    Article  PubMed  CAS  Google Scholar 

  70. Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven GM, Goldfine ID. Membrane Glycoprotein PC-1 and insulin resistance in noninsulin-dependent diabetes. Nature 1995; 373: 448–451.

    Article  PubMed  CAS  Google Scholar 

  71. Yano T, Funakoshi I, Yamashina I. Purification and properties of nucleotide pyrophosphatase J Biochem 1985; 98: 1097–1107.

    CAS  Google Scholar 

  72. Van Driel IR, Goding JW. Plasma cell membrane glycoprotein PC-1. J Biol Chem 1987; 262: 4882–4887.

    PubMed  Google Scholar 

  73. Harahap AR, Goding JW. Distribution of PC-1 in non lymphoid tissues. J. Immuno. 1988; 141: 2317–2320.

    CAS  Google Scholar 

  74. Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW. Plasma cell membrane glycoprotein PC-1 cDNA cloning of the human molecule, amino acid sequence, chromosomal location. J Biol Chem 1990; 265: 17506–17511.

    PubMed  CAS  Google Scholar 

  75. Rebbe, NF, Tong BD, Finley EM, Hickman S Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1. Proc Natl Acad Sci USA 1991; 88: 5192–5196.

    Article  PubMed  CAS  Google Scholar 

  76. Funakoshi I, Kato H, Horie K, Yano T, Hon Y, Kobayashi H, Inoue T, Suzuki H, Fukui S, Tsukahara M, Kajii T, Yamashina I. Molecular cloning of human nucleotide pyrophosphatase. Arch Biochem Biophys1992; 295: 180–187.

    Google Scholar 

  77. Uriarte M, Stalmans W, Hickman S, Bollen M. Phosphorylation and nucleotide-dependent dephosphorylation of hepatic polypeptides related to the plasma cell differentiation antigen PC-1. Biochem J 1993; 293: 93–100.

    PubMed  CAS  Google Scholar 

  78. Rebbe, NF, Tong BD, Hickman S. Expression of nucleotide pyrophosphatase and alkaline phosphodiesterase I activities of PC-1, the murine plasma cell antigen. Mol Immunol 1993; 30: 87–93.

    Article  PubMed  CAS  Google Scholar 

  79. Yoshida H, Fukui S, Funakoshi I, Yamashina I. Substrate specificity of a nucleotide pyrophosphatase responsible for the breakdown of 3’-phosphoadenosine 5’-phosphosulfate (PAPS) from human placenta. J Biochem 1983; 93: 1641–1648.

    PubMed  CAS  Google Scholar 

  80. Kawagoe H, Soma O, Goji J, Nishimura, N, Narita M, Inazawa J, Nakamura H, Sano K. Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/Nucleotide Pyrophosphotase Gene (PDNP2). Genomics 1995; 30: 380–384.

    Article  PubMed  CAS  Google Scholar 

  81. Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke M. cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterase. J Biol Chem 1994; 269: 30479–30484.

    PubMed  CAS  Google Scholar 

  82. Deisler H, Lottspeich F, Rajewsky MF. Affinity purification and cDNA cloning of rat neural differentiation and tumor cell surface antigen gp130 RB13–6 reveals relationship to human and murine PC-1. J Biol Chem 1995; 270: 9849–9855.

    Article  Google Scholar 

  83. Belli AI, Van Driel IR, Goding JW. Identification and characterization of a soluble form of the plasma cell membrane glycoprotein PC-1 (5’-nucleotide phosphodiesterase) Eur. J Biochem 1993; 217: 421–428.

    Article  PubMed  CAS  Google Scholar 

  84. Grupe A, Alleman J, Goldfine ID, Sadick M, Stewart T. Inhibition of insulin receptor phosphorylation by PC-1 is not mediated by the hydrolysis of Adenosine triphosphate or the generation of Adenosine. J Biol Chem 1995; 270: 22085–22088.

    Article  PubMed  CAS  Google Scholar 

  85. Oda Y, Kuo, M-D, Huang SS, Huang JS. The plasma cell membrane glycoprotein, PC-1, is a threonine specific protein kinase stimulated by acidic fibroblast growth factor. J Biol Chem 1991; 266: 16791–16795.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Jack F. Youngren PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ira D. Goldfine MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Trischitta MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Betty A. Maddux BS
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Shaman Pharmaceuticals, Inc., South San Francisco, CA, USA

    Gerald M. Reaven MD

  2. Stanford University School of Medicine, Stanford, CA, USA

    Gerald M. Reaven MD

  3. Stanford University School of Medicine, Stanford, CA, USA

    Ami Laws MD

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Youngren, J.F., Goldfine, I.D., Trischitta, V., Maddux, B.A. (1999). Insulin Resistance and Inhibitors of Insulin Receptor Tyrosine Kinase. In: Reaven, G.M., Laws, A. (eds) Insulin Resistance. Contemporary Endocrinology, vol 12. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-716-1_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-716-1_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-086-1

  • Online ISBN: 978-1-59259-716-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation