Monitoring of Diabetic Late Complication

  • Günter Müller
Living reference work entry


Secondary symptoms of long-lasting diabetes mellitus are diabetic neuropathy with sensory symptoms, motoric disturbances due to reduced nerve conduction velocity, and diabetic cataracts. Both are related to enhanced conversion of glucose to polyols, such as sorbitol, by the enzyme aldose reductase (van Heyningen 1959; Clements 1979). Sorbitol is converted to fructose by sorbitol dehydrogenase. A low activity of this enzyme enhances the accumulation of sorbitol, thus contributing to cellular damage. Inhibitors of aldose reductase have been developed with positive results in diabetic patients (Kador et al. 1985).


Aldose Reductase Nerve Conduction Velocity Aldose Reductase Inhibitor Adipocyte Size Motor Nerve Conduction Velocity 
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

Aldose Reductase Activity

  1. Cameron NE, Cotter MA, Robertson S (1989) Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition. Diabetologia 32:365–370PubMedGoogle Scholar
  2. Clements RS (1979) Diabetic neuropathy – new concepts in its etiology. Diabetes 28:604–611PubMedGoogle Scholar
  3. Geisen K, Utz R, Grotsch H, Lang HJ, Nimmesgern H (1994) Sorbitol-accumulating pyrimidine derivatives. Arzneim Forsch/Drug Res 44:1032–1043Google Scholar
  4. Kador PF, Robison WG, Kinoshita JH (1985) The pharmacology of aldose reductase inhibitors. Annu Rev Pharmacol Toxicol 25:691–714PubMedGoogle Scholar
  5. Pugliese G, Tilton RG, Speedy A, Chang K, Province MA, Kilo C, Williamson JR (1990) Vascular filtration function in galactose-fed versus diabetic rats: the role of polyol pathway activity. Metabolism 39:690–697PubMedGoogle Scholar
  6. Sarges R, Oates PJ (1993) Aldose reductase inhibitors: recent developments. Prog Drug Res 40:99–161PubMedGoogle Scholar
  7. Tilton RG, Chang K, Weigel C, Eades D, Sherman WR, Kilo C, Williamson JR (1988) Increased ocular blood flow and 125I-albumin permeation in galactose-fed rats: inhibition by sorbinil. Invest Ophthalmol Vis Sci 29:861–868PubMedGoogle Scholar
  8. Tilton RG, Chang K, Pugliese G, Eades DM, Province MA, Sherman WR, Kilo C, Williamson JR (1989) Prevention of hemodynamic and vascular filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes 38:1258–1270PubMedGoogle Scholar
  9. van Heyningen R (1959) Formation of polyols by the lens of the rat with “sugar” cataract. Nature 184:194–195Google Scholar
  10. Williamson JR, Chang K, Tilton RG, Prater C, Jeffrey JR, Weigel C, Sherman WR, Eades DM, Kilo C (1987) Increased vascular permeability in spontaneously diabetic BB/W rats and rats with mild versus severe streptozotocin-induced diabetes. Diabetes 36:813–821PubMedGoogle Scholar

Measurement with Normal Lenses

  1. Billon F, Delchambre C, Cloarec A, Sartori E, Teulon JM (1990) Aldose reductase inhibition by 2,4-oxo and thioxo derivates of 1,2,3,4-tetrahydroquinazoline. Eur J Med Chem 25:121–126Google Scholar
  2. Hayman S, Kinoshita JH (1965) Isolation and properties of lens aldose reductase. J Biol Chem 240:877–882PubMedGoogle Scholar
  3. Varma S, Kinoshita JH (1976) Inhibition of lens aldose reductase by flavonoids – their possible role in the prevention of diabetic cataracts. Biochem Pharmacol 25:2505–2513Google Scholar

Measurement with Cataract Lenses

  1. Gonzales AM, Sochor M, Hothersall JS, McLean P (1986) Effect of aldose reductase inhibitor (sorbinil) on integration of polyol pathway, pentose phosphate pathway and glycolytic route in diabetic rat lens. Diabetes 35:1200–1205Google Scholar
  2. Mackic JB, Ross-Cisneros FN, McComb JG, Bekhor I, Weiss MH, Kannan R, Zlokovic BV (1994) Galactose-induced cataract formation in guinea pigs: morphologic changes and accumulation of galactitol. Invest Ophthalmol Vis Sci 35:804–810PubMedGoogle Scholar
  3. Meydani M, Martin A, Sastre J, Smith D, Dallal G, Taylor A, Blumberg J (1994) Dose-response characteristics of galactose-induced cataract in the rat. Ophthalmic Res 26:368–374PubMedGoogle Scholar
  4. Naeser et al (1988) Sorbitol metabolism in the retina, optic nerve, and sural nerve of diabetic rats treated with an aldose reductase inhibitor. Metabolism 37:1143–1145Google Scholar
  5. Ohta Y, Yamasaki T, Niwa T, Goto H, Majima Y, Ishiguro I (1999) Cataract development in 12-months-old rats fed a 25% galactose diet and its relation to osmotic stress and oxidative damage. Ophthalmic Res 31:321–331PubMedGoogle Scholar
  6. Sakagami K, Igarashi H, Tanaka K, Yoshida A (1999) Organophosphate metabolic changes in the rat lens during the development of galactose-induced cataract. Hokkaido J Med Sci 74:457–466PubMedGoogle Scholar
  7. Sato S, Mori K, Wyman M, Kador FP (1998) Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175. Exp Eye Res 66:217–222PubMedGoogle Scholar

Nerve Conduction Velocity

  1. Cameron NE, Cotter MA (2003) The effects of 5-hydroxytryptamine 5-HT2 receptor antagonists on nerve conduction velocity and endoneurial perfusion in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 367:607–614PubMedGoogle Scholar
  2. Cameron NE, Cotter MA, Low AP (1991) Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 261:E1–E8PubMedGoogle Scholar
  3. Carrington AL, Ettlinger CB, Calcutt NA, Tomlinson DR (1991) Aldose reductase inhibition with imirestat-effects on impulse conduction and insulin-stimulation of Na+/K+-adenosine triphosphatase activity in sciatic nerves of streptozotocin-diabetic rats. Diabetologia 34:397–401PubMedGoogle Scholar
  4. Mayer JH, Tomlinson DR (1983) Prevention of defects of axonal transport and nerve conduction velocity by oral administration of myo-inositol or an aldose reductase inhibitor in streptozotocin-diabetic rats. Diabetologia 25:433–438PubMedGoogle Scholar
  5. Miyoshi T, Goto I (1973) Serial in vivo determinations of nerve conduction velocity in rat tails. Physiological and pathological changes. Electroencephalogr Clin Neurophysiol 35:125–131PubMedGoogle Scholar
  6. Price DE, Airey CM, Alani SM, Wales JK (1988) Effect of aldose reductase inhibition on nerve conduction velocity and resistance to ischemic conduction block in experimental diabetes. Diabetes 37:969–973Google Scholar
  7. Schmidt RE, Plurad SB, Coleman BD, Williamson JR, Tilton RG (1991) Effects of sorbinil, dietary myo-inositol supplementation, and insulin on resolution of neuroaxonal dystrophy in mesenteric nerves of streptozotocin-induced diabetic rats. Diabetes 40:573–582Google Scholar
  8. Sharma AK, Thomas PK (1974) Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 23:1–15PubMedGoogle Scholar
  9. Sima AAF, Prashar A, Zhang WX, Chakrabarti S, Greene DA (1990) Preventive effect of long-term aldose reductase inhibition (Ponalrestat) on nerve conduction and sural nerve structure in the spontaneously diabetic bio-breeding rat. J Clin Invest 85:1410–1420PubMedCentralPubMedGoogle Scholar
  10. Stribling D, Mirrlees DJ, Harrison HE, Earl DCN (1985) Properties of ICI 128,436, a novel aldose reductase inhibitor and its effects on diabetic complications in the rat. Metabolism 34:336–344PubMedGoogle Scholar
  11. Tomlinson DR, Holmes PR, Mayer JH (1982) Reversal, by treatment with an aldose reductase inhibitor, of impaired axonal transport and motor nerve conduction velocity in experimental diabetes mellitus. Neurosci Lett 31:189–193PubMedGoogle Scholar
  12. Tomlinson DR, Moriarty RJ, Mayer JH (1984) Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil. Diabetes 33:470–476Google Scholar
  13. Yue DK, Hanwell MA, Satchell PM, Turtle JR (1982) The effect of aldose inhibition on motor nerve conduction velocity in diabetic rats. Diabetes 31:789–794PubMedGoogle Scholar

Nerve Blood Flow (Doppler Flux); Electroretinogram

  1. Calcutt NA, Mizisin AP, Kalichman MW (1994) Aldose reductase inhibition, Doppler flux and conduction in diabetic rat nerve. Eur J Pharmacol 251:27–33PubMedGoogle Scholar
  2. De la Cruz J, Arrebola M, González-Correa J, Martinez-Cerdán E, Moreno A, de la Cuesta SF (2003) Effects of clopidogrel and ticlopidine on experimental ischemic retinopathy in rats. Naunyn Schmiedebergs Arch Pharmacol 367:204–210Google Scholar
  3. Engerman RL (1989) Pathogenesis of diabetic retinopathy. Diabetes 38:1203–1206PubMedGoogle Scholar
  4. Hotta N, Kakuta H, Fukasawa H, Koh N, Matsumae H, Kimura M, Sakamoto N (1988) Prevention of diabetic neuropathy by an aldose reductase inhibitor in fructose-fed streptomycin-diabetic rats. In: Sakamoto N, Kinoshita JH, Kador PF, Hotta N (eds) Polyol pathway and its role in diabetic complications. Excerpta Medica, Amsterdam, pp 311–318Google Scholar
  5. Lightman S, Rechthand E, Terubayashi H, Palestine A, Rapoport A, Kador P (1987) Permeability changes in blood-retinal barrier of galactosemic rats are prevented by aldose reductase inhibitors. Diabetes 36:1271–1275PubMedGoogle Scholar
  6. Nagata M, Robison WG (1988) Basement membrane thickening in retina and muscle of animal models of diabetes. In: Sakamoto N, Kinoshita JH, Kador PF, Hotta N (eds) Polyol pathway and its role in diabetic complications. Excerpta Medica, Amsterdam, pp 276–285Google Scholar
  7. Segawa M, Hirata Y, Fujimori S, Okada K (1988a) The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia. Metabolism 37:454–460PubMedGoogle Scholar
  8. Segawa M, Takahashi N, Namiki H, Masuzawa K (1988b) Electrophysiological abnormalities and polyol accumulation in retinas of diabetic and galactosemic rats. In: Sakamoto N, Kinoshita JH, Kador PF, Hotta N (eds) Polyol pathway and its role in diabetic complications. Excerpta Medica, Amsterdam, pp 306–310Google Scholar

Streptozotocin-Induced Cataract

  1. Dvornik D, Simard-Duquesne KM, Sestanj K, Gabbay KH, Kinoshita JH, Varma SD, Merola LO (1973) Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor. Science 182:1146–1148PubMedGoogle Scholar
  2. Griffin BW, Chandler ML, DeSantis L (1984) Prevention of diabetic cataract and neuropathy in rats by two new aldose reductase inhibitors. Invest Ophthalmol Vis Sci 25:136Google Scholar
  3. Kinoshita JH (1965) Cataracts in galactosemia. Invest Ophthalmol 4:786–799PubMedGoogle Scholar
  4. Kinoshita JH (1974) Mechanisms initiating cataract formation. Invest Ophthalmol 13:713–724PubMedGoogle Scholar
  5. Kinoshita JH, Fukushi S, Kador P, Merola LO (1979) Aldose reductase in diabetic complications of the eye. Metabolism 28(Suppl 1):462–469PubMedGoogle Scholar
  6. Müller P, Hockwin O, Ohrloff C (1985) Comparison of aldose reductase inhibitors by determination of IC50 with bovine and rat lens extracts. Ophthalmic Res 17:115–119PubMedGoogle Scholar
  7. Pirie A, van Heyningen R (1964) Effect of diabetes on the content of sorbitol, glucose, fructose and inositol in the human lens. Exp Eye Res 3:124–131PubMedGoogle Scholar
  8. van Heyningen R (1959) Formation of polyols by the lens of the rat with “sugar” cataract. Nature 184:194–195Google Scholar
  9. Varma SD, Kinoshita JH (1976) Inhibition of lens aldose reductase by flavonoids – their possible role in the prevention of diabetic cataracts. Biochem Pharmacol 25:2505–2513Google Scholar
  10. Wegener A, Hockwin O (1991) Benefit/risk assessment of ophthalmic anti-infectives. Chibret Intern J Ophthalmol 8:43–45Google Scholar

Naphthalene-Induced Cataract

  1. Hockwin O (1989) Die Scheimpflug-Photographie der Linse. Fortschr Ophthalmol 86:304–311PubMedGoogle Scholar
  2. Hockwin O, Wegener A, Sisk DR, Dohrmann B, Kruse M (1985) Efficacy of AL-1576 in preventing naphthalene cataract in three rat strains. Slit lamp and Scheimpflug photographic study. Lens Res 2:321–335Google Scholar
  3. Holmen JB, Ekesten B, Lundgren B (1999) Naphthalen-induced cataract model in rats: a comparative study between slit and retroillumination images, biochemical changes and naphthalene dose and duration. Curr Eye Res 19:418–425PubMedGoogle Scholar
  4. Rathbun WB, Nagasawa HT, Killen CE (1996a) Prevention of naphthalene-induced cataract and hepatic glutathione loss by the L-cysteine prodrugs, MTCA and PTCA. Exp Eye Res 62:433–441PubMedGoogle Scholar
  5. Rathbun WB, Holleschau AM, Cohen JF, Nagasawa HT (1996b) Prevention of acetaminophen- and naphthalene-induced cataract and glutathione loss by CySSME. Invest Ophthalmol Vis Sci 37:923–929PubMedGoogle Scholar
  6. Wegener A, Hockwin O (1991) Benefit/risk assessment of ophthalmic anti-infectives. Chibret Intern J Ophthalmol 8:43–45Google Scholar

Determination of Advanced Glycation End Products (AGE); Measurement of Reactive Oxygen Species (ROS) Production

  1. Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hedge A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Du-Yan SS (2004) RAGE potentiates Abeta-induced perturbation of neuronal function on transgenic mice. EMBO J 23:4096–4105PubMedCentralPubMedGoogle Scholar
  2. Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M (1982) Flow cytometry studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 130:1910–1917Google Scholar
  3. Baynes J (1991) Role of oxidative stress in development of complications in diabetesGoogle Scholar
  4. Beisswenger PJ, Moore LL, Brinck-Johnson T, Curphey TJ (1993) Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy. J Clin Invest 92:212–217Google Scholar
  5. Brett J et al (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143:1699–1712PubMedCentralPubMedGoogle Scholar
  6. Brownlee M (1995) Advanced glycosylation in diabetes and aging. Annu Rev Med 46:223–234PubMedGoogle Scholar
  7. Cayot P, Tainturier G (1997) The quantification of protein amino groups by the trinitrobenzenesulfonic acid method: a reexamination. Anal Biochem 249:184–200PubMedGoogle Scholar
  8. Degli Esposti M, Hatzinisiriou I, McLennan H, Ralph S (1999) Bcl-2 and mitochondrial oxygen radicals. J Biol Chem 274:29831–29837Google Scholar
  9. Freeman H, Shimomura K, Horner E, Cox RD, Ashcroft FM (2006) Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion. Cell Metab 3:35–45PubMedGoogle Scholar
  10. Greene D et al (1987) Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 316:599–606PubMedGoogle Scholar
  11. Greenwood PC, Hunter WM, Glover JS (1963) The preparation of 131I-labeled human growth hormone of high specific radioactivity. Biochem J 89:114–123PubMedCentralPubMedGoogle Scholar
  12. Hadding A, Kaltschmidt B, Kaltschmidt C (2004) Overexpression of receptor of advanced glycation end products hypersensitizes cells for amyloid beta peptide-induced cell death. Biochim Biophys Acta 1691:67–72PubMedGoogle Scholar
  13. Holley AE, Cheeseman KH (1993) Measuring free radical reactions in vivo. Br Med Bull 49:494–505PubMedGoogle Scholar
  14. Ikeda K, Higashi T, Sano H, Jinnouchi Y, Yoshida M, Araki T, Ueda S, Horiuchi S (1996) Carboxymethyllysine protein adduct is a major immunological epitope in proteins modified with AGEs of the Maillard reaction. Biochemistry 35:8075–8083PubMedGoogle Scholar
  15. Inoguchi T et al (1994) Insulin’s effect on protein kinase C and diacylglycerol induced by diabetes and glucose in vascular tissues. Am J Physiol 267:E369–E379PubMedGoogle Scholar
  16. Keston AS, Brandt R (1965) The fluorometric analysis of ultramicro quantities of hydrogen peroxide. Anal Biochem 11:1–5PubMedGoogle Scholar
  17. Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Yan SD, Hofmann M, Yan SF, Pischetsrieder M, Stern D, Schmidt AM (1999a) N-(Carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation products that activate cell signaling pathways and modulate gene expression. J Biol Chem 274:31740–31749PubMedGoogle Scholar
  18. Kislinger T et al (1999b) N-(carboxy-methyl)lysine modifications of proteins are ligands for RAGE that activate cell signaling pathways and modulate gene expression. J Biol Chem 274:31740–31749PubMedGoogle Scholar
  19. Klotz I, Hunston D (1984) Mathematical models for ligand-receptor binding. Real sites, ghost sites. J Biol Chem 259:10060–10062PubMedGoogle Scholar
  20. Koya D, King G (1998) PKC activation and the development of diabetic complications. Diabetes 47:859–866PubMedGoogle Scholar
  21. LeBel CP, Ishiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescein as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231PubMedGoogle Scholar
  22. Miyata T et al (1996) RAGE mediates the interaction of AGE-beta-2-microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway: implications for the pathogenesis of dialysis-related amyloidosis. J Clin Invest 98:1088–1094PubMedCentralPubMedGoogle Scholar
  23. Neeper M et al (1992) Cloning and expression of RAGE: a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004PubMedGoogle Scholar
  24. Nishikawa et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycemic damage. Nature 404:787–790PubMedGoogle Scholar
  25. Oldfield MD, Bach LA, Forbes JM, Nikolic-Paterson D, McRoberts A, Thallas V, Atkins RC, Osicka T, Jerums G, Cooper ME (2001) Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest 108:1853–1863PubMedCentralPubMedGoogle Scholar
  26. Reddy S et al (1995) Carboxymethyllysine is a dominant AGE antigen in tissue proteins. Biochemistry 34:10872–10878PubMedGoogle Scholar
  27. Ruderman N et al (1992) Glucose and diabetic vascular disease. FASEB J 6:2905–2914PubMedGoogle Scholar
  28. Russell JW, Golovoy D, Vincent AM, Mahendru P, Olzmann JA, Mentzer A, Feldman EL (2002) High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J 16:1738–1748PubMedGoogle Scholar
  29. Schmidt AM, Stern D (2000a) A radical approach to the pathogenesis of diabetic complications. Trends Pharmacol Sci 21:367–369PubMedGoogle Scholar
  30. Schmidt AM, Stern DM (2000b) RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes. Trends Endocrinol Metab 11:368–375PubMedGoogle Scholar
  31. Schmidt AM et al (1992) Isolation and characterization of binding proteins for advanced glycosylation end products from lung tissue which are present on the endothelial cell surface. J Biol Chem 267:14987–14997PubMedGoogle Scholar
  32. Sell D et al (1992) Pentosidine formation in skin correlates with severity of complications in individuals with longstanding IDDM. Diabetes 41:1286–1292PubMedGoogle Scholar
  33. Skolnik EY et al (1991) Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy. J Exp Med 174:931–939PubMedGoogle Scholar
  34. Soulis T et al (1997) Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury. Diabetologia 40:619–628PubMedGoogle Scholar
  35. Vlassara H, Brownlee M, Cerami A (1985) High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci U S A 82:5588–5592PubMedCentralPubMedGoogle Scholar
  36. Vlassara H et al (1995) Galectin-2 as a high affinity binding protein for AGE: a new member of the AGE-receptor complex. Mol Med 1:634–646PubMedCentralPubMedGoogle Scholar
  37. Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616PubMedGoogle Scholar
  38. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 139:1281–1292PubMedCentralPubMedGoogle Scholar
  39. Wolvetang EJ, Johnson KL, Krauer K, Ralph SJ, Linnane AW (1994) Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett 339:40–44PubMedGoogle Scholar
  40. Xia P et al (1994) Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes 43:1122–1129PubMedGoogle Scholar
  41. Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, Watanabe T, Yamagishi SI, Sakurai S, Takasawa S, Okamoto H, Yamamoto H (2001) Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 108:261–268PubMedCentralPubMedGoogle Scholar

Communication Between Metabolically Relevant Cells

  1. Abbasi F, Chu JW, Lamendola C et al (2004) Discrimination between obesity and insulin resistance in the relationship with adiponectin. Diabetes 53:585–590PubMedGoogle Scholar
  2. Aboulaich N, Vener AV, Stralfors P (2006) Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes. J Biol Chem 281:11446–11449PubMedGoogle Scholar
  3. Aoki N, Jin-no S, Nakagawa Y et al (2007) Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and hormone-dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles. Endocrinology 148:3850–3862PubMedGoogle Scholar
  4. Arner P (2010) Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59:105–109PubMedCentralPubMedGoogle Scholar
  5. Bahceci M, Gokalp D, Bahceci S (2007) The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6, and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J Endocrinol Invest 30:210–214PubMedGoogle Scholar
  6. Baldassarri S, Bertoni A, Bagarotti A et al (2008) The endocannabinoid 2-arachidonylglycerol activates human platelets through non-CB1/CB2 receptors. J Thromb Haemost 6:1772–1779PubMedGoogle Scholar
  7. Baldo A, Sniderman AD, St-Luce S et al (1993) The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis. J Clin Invest 92:1543–1547PubMedCentralPubMedGoogle Scholar
  8. Benelli R, Adatia R, Ensoli B et al (1994) Inhibition of AIDS-Kaposi’s sarcoma cell induced endothelial cell invasion by TIMP-2 and a synthetic peptide from the metalloproteinase propeptide: implications for an anti-angiogenic therapy. Oncol Res 6:251–257PubMedGoogle Scholar
  9. Björntorp P (1974) Effects of age, sex, and clinical conditions on adipose tissue cellularity in man. Metabolism 23:1091–1102PubMedGoogle Scholar
  10. Björntorp P, Karlsson M (1970) Triglyceride synthesis in human subcutaneous adipose tissue cells of different size. Eur J Clin Invest 1:112–117PubMedGoogle Scholar
  11. Björntorp P, Carlgren G, Isaksson B et al (1975) Effect of an energy reduced dietary regimen in relation to adipose tissue cellularity in obese women. Am J Clin Nutr 28:445–452PubMedGoogle Scholar
  12. Blouin CM, Le Lay SL, Lasnier F et al (2008) Regulated association of caveolins to lipid droplets during differentiation of 3T3-L1 adipocytes. Biochem Biophys Res Commun 376:331–335PubMedGoogle Scholar
  13. Blüher M, Michael MD, Peroni OD et al (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 3:25–38PubMedGoogle Scholar
  14. Boucharaba A, Serre CM, Grès S, Saulnier-Blache JS, Bordet JC, Guglielmi J, Clézardin P, Peyruchaud O (2004) Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 114:1714–1725PubMedCentralPubMedGoogle Scholar
  15. Brown DA (1992) Interactions between GPI-anchored proteins and membrane lipids.Trends Cell Biol 2:338–343Google Scholar
  16. Brown DA, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14:111–136PubMedGoogle Scholar
  17. Brown LM, Fox HL, Hazen SA et al (1997) Role of the matrix MMP-2 in multicellular organization of adipocytes cultured in basement membrane components. Am J Physiol 272:C937–C949PubMedGoogle Scholar
  18. Burnstock G (2002) Purinergic signalling and vascular cell proliferation and death. Arterioscler Thromb Vasc Biol 22:364–373PubMedGoogle Scholar
  19. Cawthorn WP, Sethi JK (2008) TNF-α and adipocyte biology. FEBS Lett 582:117–131PubMedCentralPubMedGoogle Scholar
  20. Chavez JA, Summers SA (2010) Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochim Biophys Acta 1801:252–265PubMedCentralPubMedGoogle Scholar
  21. Christodoulides C, Lagathu C, Sethi JK et al (2008) Adipogenesis and WNT signalling. Trends Endocrinol Metab 20:16–24PubMedCentralPubMedGoogle Scholar
  22. Cinti S, Mitchell G, Barbatelli G (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMedGoogle Scholar
  23. Coleman RA, Lewin TM, Muoio DM (2000) Physiological and nutritional regulation of enzymes of triacylglycerol synthesis. Annu Rev Nutr 20:77–103PubMedGoogle Scholar
  24. Coppinger JA, Cagney G, Toomey S et al (2004) Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 103:2096–2104PubMedGoogle Scholar
  25. Cornelius P, MacDonald OA, Lane MD (1994) Regulation of adipocyte development. Annu Rev Nutr 14:99–129PubMedGoogle Scholar
  26. Cushman SW, Salans LB (1978) Determination of adipose cell size and number in suspensions of isolated rat and human adipose cells. J Lipid Res 19:269–273PubMedGoogle Scholar
  27. Danforth E (2000) Failure of adipocyte differentiation causes type II diabetes mellitus ? Nat Genet 26:13PubMedGoogle Scholar
  28. DeFronzo RA (2004) Dysfunctional fat cells, lipotoxicity and type 2 diabetes. Int J Clin Pract Suppl 143:9–21PubMedGoogle Scholar
  29. Despres JP, Bouchard C, Savard R (1984) Level of physical fitness and adipocyte lipolysis in humans. J Appl Physiol 56:1157–1161PubMedGoogle Scholar
  30. Dugail I, Hajduch E (2007) A new look at adipocyte lipid droplets : towards a role in the sensing of triacylglycerol stores ? Cell Mol Life Sci 64:2452–2458PubMedGoogle Scholar
  31. Dugail I, Le Lay S, Varret M et al (2003) New insights into how adipocytes sense their triglyceride stores. Is cholesterol a signal? Horm Metab Res 35:204–210PubMedGoogle Scholar
  32. Elimam A, Kamel A, Marcus C (2002) In vitro effects of leptin on human adipocyte metabolism. Horm Res 58:88–93PubMedGoogle Scholar
  33. Famulla S, Lamers D, Hartwig S et al (2011) Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int J Obes 35:762–772Google Scholar
  34. Fasshauer M, Blüher M (2015) Adipokines in health and disease. Trends Pharmacol Sci doi:10.1016/ Scholar
  35. Faust IM, Johnson PR, Stern JS et al (1978) Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol 4:E279–E286Google Scholar
  36. Frühbeck G, Aguado M, Martinez JA (1997) In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochim Biophys Acta 240:590–594Google Scholar
  37. Goralski KB, McCarthy TC, Hanniman E et al (2007) Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 282:28175–28188PubMedGoogle Scholar
  38. Grenegard M, Vretenbrant-Oberg K, Nylander N et al (2008) The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine. J Biol Chem 283:18493–18504PubMedGoogle Scholar
  39. Guo KY, Halo P, Leibel RL et al (2004) Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol Regul Integr Comp Physiol 287:R112–R119PubMedGoogle Scholar
  40. Häger A, Sjörström L, Arvidsson B et al (1978) Adipose tissue cellularity in obese school girls before and after dietary intervention. Am J Clin Nutr 31:68–75PubMedGoogle Scholar
  41. Han CY, Kargi AY, Omer M et al (2010) Differential effect of saturated and unsaturated free FA on the generation of monocyte adhesion and chemotactic factors by adipocytes. Diabetes 59:386–396Google Scholar
  42. Hauner H (2005) Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc 64:163–169PubMedGoogle Scholar
  43. Hauner H (2010) Adipose tissue inflammation: are small or large fat cells to blame? Diabetologia 53:223–225PubMedGoogle Scholar
  44. Hazen SA, Rowe WA, Lynch CJ (1995) Monolayer cell culture of freshly isolated adipocytes using extracellular basement membrane components. J Lipid Res 36:868–875PubMedGoogle Scholar
  45. Hirsch J, Batchelor B (1976) Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5:299–311PubMedGoogle Scholar
  46. Hirsch J, Knittle JL (1970) Cellularity of obese and nonobese human adipose tissue. Fed Proc 29:1516–1521PubMedGoogle Scholar
  47. Holm G, Jacobsson B, Bjorntop P et al (1975) Effects of age and cell size on rat adipose tissue metabolism. J Lipid Res 16:461–464PubMedGoogle Scholar
  48. Horvath I, Multhoff G, Sonnleitner A et al (2008) Membrane-associated stress proteins: more than simply chaperones. Biochim Biophys Acta 1778:1653–1664PubMedGoogle Scholar
  49. Hotta K, Funahashi T, Bodkin NL (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133PubMedGoogle Scholar
  50. Jacobi SK, Ajuwon KM, Weber TE et al (2004) Cloning and expression of porcine adiponectin, and its relationship to adiposity, lipogenesis and the acute phase response. J Endocrinol 182:133–144PubMedGoogle Scholar
  51. Johannes L, Mayor S (2010) Induced domain formation in endocytic invagination, lipid sorting, and scission. Cell 142:507–510PubMedGoogle Scholar
  52. Julien P, Despres J-P, Angel A (1989) Scanning electron microscopy of very small fat cells in human obesity. J Lipid Res 30:293–299PubMedGoogle Scholar
  53. Kahner BN, Shankar H, Murugappan S et al (2006) Nucleotide receptor signaling in platelets. J Thromb Haemost 4:2317–2326PubMedGoogle Scholar
  54. Kashiwagi A, Mott D, Bogardus C et al (1985) The effects of short-term overfeeding on adipocyte metabolism in Pima Indians. Metabolism 34:364–370PubMedGoogle Scholar
  55. Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634PubMedGoogle Scholar
  56. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556PubMedGoogle Scholar
  57. Kiess W, Petzold S, Töpfer M et al (2008) Adipocytes and adipose tissue. Best Pract Clin Endocrinol Metab 22:135–153Google Scholar
  58. Klimcakova E, Kovacikova M, Stich V et al (2010) Adipokines and dietary interventions in human obesity. Obes Rev 11:446–456PubMedGoogle Scholar
  59. Kulkarni S, Woollard KJ, Thomas S et al (2007) Conversion of platelets from a proaggregatory to a proinflammatory adhesive phenotype: role of PAF in spatially regulating neutrophil adhesion and spreading. Blood 110:1879–1886PubMedGoogle Scholar
  60. Lamers D, Famulla S, Wronkowitz N et al (2011) Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60:1917–1925PubMedCentralPubMedGoogle Scholar
  61. Langin D (2006) Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res 53:482–491PubMedGoogle Scholar
  62. Le Lay S, Dugail I (2009) Connecting lipid droplet biology and the metabolic syndrome. Prog Lipid Res 48:191–195PubMedGoogle Scholar
  63. Le Lay S, Hajduch E, Lindsay MR et al (2006) Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role for caveolar endocytosis. Traffic 7:549–561PubMedGoogle Scholar
  64. Le Lay S, Blouin CM, Hajduch E et al (2008) Filling up adipocytes with lipids. Lessons from caveolin-1 deficiency. Biochim Biophys Acta 1791:514–518PubMedGoogle Scholar
  65. Lefebvre JS, Marleau S, Milot V et al (2010) Toll-like receptor ligands induce polymorphonuclear leukocyte migration: key roles for leukotriene B4 and platelet-activating factor. FASEB J 24:637–647PubMedGoogle Scholar
  66. Lehr S, Hartwig S, Lamers D et al (2011) Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics. doi:10.1074/mcp.M111.010504PubMedCentralPubMedGoogle Scholar
  67. Lundgren M, Svensson M, Lindmark S (2007) Fat cell enlargement is an independent marker of insulin resistance and “hyperleptinemia”. Diabetologia 50:625–633PubMedGoogle Scholar
  68. Martin S, Parton RG (2006) Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol 7:373–378PubMedGoogle Scholar
  69. Martin S, Pol A (2005) Caveolin, cholesterol, and lipid bodies. Semin Cell Dev Biol 16:163–174PubMedGoogle Scholar
  70. McLaughlin T, Allison G, Abbasi F et al (2004) Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals. Metabolism 53:495–499PubMedGoogle Scholar
  71. McLaughlin T, Sherman A, Tsao P et al (2007) Enhanced proportion of small adipose cells in insulin-resistant vs. insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia 50:1707–1715PubMedGoogle Scholar
  72. McLaughlin T, Deng A, Yee G et al (2010) Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia 53:369–377PubMedGoogle Scholar
  73. Monteiro R, Calhau C, Azevedo I (2006) Adipocyte size and liability to cell death. Obes Surg 16:804–806PubMedGoogle Scholar
  74. Monteiro R, Calhau C, Azevedo I (2007) Comment on: Tchoukalova Y, Koutsari C, Jensen M (2007) Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 50:151–157Google Scholar
  75. Müller G (2010) Control of lipid storage and cell size between adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins. Arch Physiol Biochem 117:23–43PubMedGoogle Scholar
  76. Müller G, Ertl J, Gerl M et al (1997) Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 272:10585–10593PubMedGoogle Scholar
  77. Müller G, Hanekop N, Wied S et al (2002) 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
  78. Müller G, Schulz A, Wied S et al (2005) Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes. Biochem Pharmacol 69:761–780PubMedGoogle Scholar
  79. Müller G, Wied S, Jung C et al (2008a) Translocation of glycosylphosphatidylinositol-anchored proteins to lipid droplets and inhibition of lipolysis in rat adipocytes is mediated by reactive oxygen species. Br J Pharmacol 154:901–913PubMedCentralPubMedGoogle Scholar
  80. Müller G, Wied S, Jung C et al (2008b) Coordinated regulation of esterification and lipolysis by palmitate, H2O2 and the anti-diabetic sulfonylurea drug, glimepiride, in rat adipocytes. Eur J Pharmacol 597:6–18PubMedGoogle Scholar
  81. Müller G, Wied S, Over S et al (2008c) Inhibition of lipolysis by palmitate, H2O2 and the sulfonylurea drug, glimepiride, in rat adipocytes depends on cAMP degradation by lipid droplets. Biochemistry 47:1259–1273PubMedGoogle Scholar
  82. Müller G, Wied S, Walz N et al (2008d) Translocation of glycosylphosphatidylinositol-anchored proteins from plasma membrane microdomains to lipid droplets in rat adipocytes is induced by palmitate, H2O2 and the sulfonylurea drug, glimepiride. Mol Pharmacol 73:1513–1529PubMedGoogle Scholar
  83. Müller G, Jung C, Straub J et al (2009a) Induced release of membrane vesicles and exosomes from rat adipocytes containing lipid droplet, lipid raft and glycosylphosphatidylinositol-anchored proteins. Cell Signal 21:324–338PubMedGoogle Scholar
  84. Müller G, Jung C, Wied S et al (2009b) Induced translocation of glycosylphosphatidylinositol-anchored proteins from lipid droplets to microvesicles in rat adipocytes. Br J Pharmacol 158:749–770PubMedCentralPubMedGoogle Scholar
  85. Müller G, Wied S, Dearey E-A et al (2010a) Lipid storage in large and small rat adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins. In: Richter W, Beisiegel U, Joost U, Meyerhof P (eds) Results and problems in cell differentiation: sensory and metabolic control of energy balance, vol 52. Springer Press, Berlin/Heidelberg/New York, pp 27–34Google Scholar
  86. Müller G, Wied S, Jung C et al (2010b) Transfer of glycosylphosphatidylinositol-anchored 5′-nucleotidase CD73 from microvesicles into rat adipocytes stimulates lipid synthesis. Br J Pharmacol 160:878–891PubMedCentralPubMedGoogle Scholar
  87. Müller G, Wied S, Jung C et al (2010c) Inhibition of lipolysis by microvesicles containing glycosylphosphatidylinositol-anchored Gce1 protein in rat adipocytes. Arch Physiol Biochem 116:28–41PubMedGoogle Scholar
  88. Müller G, Wied S, Dearey E-A et al (2011) Glycosylphosphatidylinositol-anchored proteins coordinate lipolysis inhibition between large and small adipocytes. Metabolism 60:1021–1037PubMedGoogle Scholar
  89. Nosjean O, Briolay A, Roux B (1997) Mammalian GPI proteins: sorting, membrane residence and functions. Biochim Biophys Acta 1331:153–186PubMedGoogle Scholar
  90. Nurden AT, Nurden P, Sanchez M et al (2008) Platelets and wound healing. Front Biosci 13:3525–3548Google Scholar
  91. Olefsky JM (1977) Insensitivity of large rat adipocytes to the antilipolytic effects of insulin. J Lipid Res 18:59–64Google Scholar
  92. Ouchi N, Higuchi A, Ohashi K et al (2010) Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science 329:454–457PubMedCentralPubMedGoogle Scholar
  93. Panetti TS, Hannah DF, Avraamides C et al (2004) Extracellular matrix regulate endothelial cell migration stimulated by lysophosphatidic acid. J Thromb Haemost 2:1645–1656PubMedGoogle Scholar
  94. Pasarica M, Tchoukalova YD, Heilbronn LK et al (2009) Differential effect of weight loss on adipocyte size subfractions in patients with type 2 diabetes. Obesity 17:1976–1978PubMedCentralPubMedGoogle Scholar
  95. Päth G, Bornstein SR, Gurniak M et al (2001) Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function. J Clin Endocrinol Metab 86:2281–2288PubMedGoogle Scholar
  96. Petersen EW, Carey AL, Sacchetti M et al (2005) Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. Am J Physiol Endocrinol Metab 288:E155–E162PubMedGoogle Scholar
  97. Pfeiffer AFH (2007) Adipose tissue and diabetes therapy: do we hit the target ? Horm Metab Res 39:734–738PubMedGoogle Scholar
  98. Pilch PF, Bergenheim N (2006) Pharmacological targeting of adipocytes/fat metabolism for treatment of obesity and diabetes. Mol Pharmacol 70:779–785PubMedGoogle Scholar
  99. Pol A, Martin S, Fernandez MA et al (2005) Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies. Mol Biol Cell 16:2091–2105PubMedCentralPubMedGoogle Scholar
  100. Pravenec M, Kazdova L, Maxova M et al (2008) Long-term pioglitazone treatment enhances lipolysis in rat adipose tissue. Int J Obes 32:1848–1853Google Scholar
  101. Rabe K, Lehrke M, Parhofer KG et al (2008) Adipokines and insulin resistance. Mol Med 14:741–751PubMedCentralPubMedGoogle Scholar
  102. Rebuffe-Scrive M, Andersson B, Olbe L et al (1989) Metabolism of adipose tissue in intraabdominal depots of nonobese men and women. Metabolism 38:453–458PubMedGoogle Scholar
  103. Reed GL (2004) Platelet secretory mechanism. Semin Thromb Hemost 30:441–450PubMedGoogle Scholar
  104. Ryden M, Arner P (2007) Tumour necrosis factor-alpha in human adipose tissue – from signalling mechanisms to clinical implications. J Intern Med 262:431–438PubMedGoogle Scholar
  105. Salans LB, Knittle JL, Hirsch J (1968) Role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J Clin Invest 47:152–165Google Scholar
  106. Saleh J, Summers LK, Cianflone K et al (1998) Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. J Lipid Res 39:884–891PubMedGoogle Scholar
  107. Savage DM, Petersen KF, Shulman GI (2005) Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension 45:828–833PubMedGoogle Scholar
  108. Sears DD, Hsiao G, Hsiao A et al (2009) Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization. Proc Natl Acad Sci U S A 106:18745–18750PubMedCentralPubMedGoogle Scholar
  109. Shadid S, Jensen MD (2003) Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care 26:3148–3152PubMedGoogle Scholar
  110. Sims EA, Goldman RF, Gluck CM et al (1968) Experimental obesity in man. Trans Assoc Am Physicians 81:153–170PubMedGoogle Scholar
  111. Skurk T, Alberti-Huber C, Herder C et al (2007) Relationships between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92:1023–1033PubMedGoogle Scholar
  112. Spalding KL, Arner E, Westermark PO et al (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedGoogle Scholar
  113. Staal FJ, Luis TC, Tiemessen MM (2008) WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 8:581–593PubMedGoogle Scholar
  114. Stern JS, Batchelor BR, Hollander N et al (1972) Adipose cell size and immunoreactive insulin levels in obese and normal weight adults. Lancet 2:948–951PubMedGoogle Scholar
  115. Takahashi M, Takahashi Y, Takahashi T et al (2008) Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett 582:573–579PubMedGoogle Scholar
  116. Takeya H, Gabazza EC, Aoki S et al (2003) Synergistic effect of sphingosine 1-phosphate on thrombin-induced tissue factor expression in endothelial cells. Blood 102:1693–1700PubMedGoogle Scholar
  117. Tchoukalova YD, Koutsari C, Jensen M (2007) Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 50:151–157PubMedGoogle Scholar
  118. Tchoukalova YD, Votruba SB, Tchkonia T et al (2010) Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci U S A 107:18226–18231PubMedCentralPubMedGoogle Scholar
  119. Torii T, Miyamoto Y, Sanbe A et al (2010) Cytohesin-2/ARNO, through its interaction with focal adhesion adaptor protein paxillin, regulates preadipocyte migration via the downstream activation of Arf6. J Biol Chem 285:24270–24281PubMedCentralPubMedGoogle Scholar
  120. Trayhurn P, Drevon CA, Eckel J (2011) Secreted proteins from adipose tissue and skeletal muscle – adipokines, myokines and adipose/muscle cross-talk. Arch Physiol Biochem 117:47–56PubMedGoogle Scholar
  121. Tsukahara T, Tsukahara R, Fujiwara Y et al (2010) Phospholipase D2-dependent inhibition of the nuclear hormone receptor PPARγ by cyclic phosphatidic acid. Mol Cell 39:421–432PubMedCentralPubMedGoogle Scholar
  122. Unger RH (2003) The physiology of cellular liporegulation. Annu Rev Physiol 65:333–347PubMedGoogle Scholar
  123. Unger RH (2005) Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie 87:57–64PubMedGoogle Scholar
  124. van den Bosch H (1974) Phosphoglyceride metabolism. Annu Rev Biochem 43:243–277PubMedGoogle Scholar
  125. Varma R, Mayor S (1998) GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394:798–801PubMedGoogle Scholar
  126. Vigh L, Horvath I, Maresca B et al (2007) Can the stress protein response be controlled by “membrane-lipid therapy”. Trends Biochem Sci 32:357–363PubMedGoogle Scholar
  127. Wang MY, Orci L, Ravazzola M et al (2005) Fat storage in adipocytes requires inactivation of leptin’s paracrine activity: implications for treatment of human obesity. Proc Natl Acad Sci U S A 102:18011–18016PubMedCentralPubMedGoogle Scholar
  128. Wang S, Liu S, Liu H et al (2010a) 20-hydroxyecdysone reduces insect food consumption resulting in fat body lipolysis during molting and pupation. J Mol Cell Biol 2:128–138PubMedGoogle Scholar
  129. Wang Y, Zhao L, Smas C et al (2010b) Pref-1 interacts with fibronectin to inhibit adipocyte differentiation. Mol Cell Biol 30:3480–3492PubMedCentralPubMedGoogle Scholar
  130. Wasserman F (1965) Handbook of physiology, adipose tissue. In: Am Physiol Soc The development of adipose tissue, Ed. by Renold AE, Cahill GF Jr, American Physiological Society, Washington, DC, pp 87–100Google Scholar
  131. Wueest S, Rapold RA, Rytka JM et al (2007) Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice. Diabetologia 52:541–546Google Scholar
  132. Yang RZ, Lee MJ, Hu H et al (2006) Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290:E1253–E1261PubMedGoogle Scholar
  133. Zhang Q, Peyruchaud O, French KJ et al (1999) Sphingosine 1-phosphate stimulates fibronectin matrix assembly through a Rho-dependent signal pathway. Blood 93:2984–2990PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Helmholtz Center MunichInstitute for Diabetes and ObesityMunichGermany

Personalised recommendations