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Diabetologia

Erschienen in:

01.06.2005 | Review

An immune origin of type 2 diabetes?

verfasst von: H. Kolb, T. Mandrup-Poulsen

Erschienen in: Diabetologia | Ausgabe 6/2005

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Abstract

Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease. This may be more than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators are associated with the disease, and the two major environmental factors the contribute to the risk of type 2 diabetes—diet and physical activity—have a direct impact on levels of systemic immune mediators. In animal models, targeting of immune genes enhanced or suppressed the development of obesity or diabetes. Obesity is associated with the infiltration and proinflammatory activity of macrophages in adipose tissue, and immune mediators may be important regulators of insulin resistance, mitochondrial function, ectopic lipid storage and beta cell dysfunction or death. Intervention studies targeting these pathways would help to determine the contribution of an activated innate immune system to the development of type 2 diabetes.

Winzler RJ (1960) Glycoproteins. In: Putnam FW (ed) The plasma proteins. London Academic, New York, p 309

Cogan DG, Merola L, Laibson PR (1961) Blood viscosity, serum hexosamine and diabetic retinopathy. Diabetes 10:393–395PubMed

Bergstrand CG, Furst P, Larsson Y, Sterky G (1962) Serum haptoglobin in juvenile diabetes. Scand J Clin Lab Invest 14:629–632PubMed

Ganrot PO, Gydell K, Ekelund H (1967) Serum concentration of alpha-2-macroglobulin, haptoglobin and alpha-1-antitrypsin in diabetes mellitus. Acta Endocrinol (Copenh) 55:537–544

Cleve H, Alexander K, Mitzkat HJ, Nissen P, Salzmann I (1968) Serum glycoproteins in diabetes mellitus; quantitative immunological determination of acid alpha 1-glycoprotein, Gc, alpha 2-macroglobulin and hemopexin in diabetics with and without angiopathy [article in German]. Diabetologia 4:48–55CrossRefPubMed

McMillan DE (1970) Changes in serum proteins and protein-bound carbohydrates in diabetes mellitus. Diabetologia 6:597–604CrossRefPubMed

Schmidt MI, Duncan BB, Sharrett AR et al (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities Study): a cohort study. Lancet 353:1649–1652CrossRefPubMed

Duncan BB, Schmidt MI, Offenbacher S, Wu KK, Savage PJ, Heiss G (1999) Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 22:767–772PubMed

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334CrossRefPubMed

10.

Barzilay JI, Abraham L, Heckbert SR et al (2001) The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. Diabetes 50:2384–2389PubMed

11.

Lindsay RS, Krakoff J, Hanson RL, Bennett PH, Knowler WC (2001) Gamma globulin levels predict type 2 diabetes in the Pima Indian population. Diabetes 50:1598–1603PubMed

12.

Vozarova B, Weyer C, Lindsay RS, Pratley RE, Bogardus C, Tataranni PA (2002) High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51:455–461PubMed

13.

Freeman DJ, Norrie J, Caslake MJ et al (2002) C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51:1596–1600PubMed

14.

Ford ES (2002) Leukocyte count, erythrocyte sedimentation rate, and diabetes incidence in a national sample of US adults. Am J Epidemiol 155:57–64CrossRefPubMed

15.

Nakanishi N, Yoshida H, Matsuo Y, Suzuki K, Tatara K (2002) White blood-cell count and the risk of impaired fasting glucose or type II diabetes in middle-aged Japanese men. Diabetologia 45:42–48CrossRefPubMed

16.

Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMed

17.

Thorand B, Lowel H, Schneider A et al (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg Cohort Study, 1984–1998. Arch Intern Med 163:93–99CrossRefPubMed

18.

Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817PubMed

19.

Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean ME, Haffner SM (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25:2016–2021PubMed

20.

Tan KC, Wat NM, Tam SC, Janus ED, Lam TH, Lam KS (2003) C-reactive protein predicts the deterioration of glycemia in Chinese subjects with impaired glucose tolerance. Diabetes Care 26:2323–2328PubMed

21.

Hu FB, Meigs JB, Li TY, Rifai N, Manson JE (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700PubMed

22.

Snijder MB, Dekker JM, Visser M et al (2003) Prospective relation of C-reactive protein with type 2 diabetes: response to Han et al. Diabetes Care 26:1656–1657PubMed

23.

Groop L, Groop PH, Koskimies S (1986) Relationship between B-cell function and HLA antigens in patients with type 2 (non-insulin-dependent) diabetes. Diabetologia 29:757–760CrossRefPubMed

24.

Rich SS, French LR, Sprafka JM, Clements JP, Goetz FC (1993) HLA-associated susceptibility to type 2 (non-insulin-dependent) diabetes mellitus: the Wadena City Health Study. Diabetologia 36:234–238CrossRefPubMed

25.

Tuomilehto-Wolf E, Tuomilehto J, Hitman GA et al (1993) Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region. BMJ 307:155–159PubMed

26.

Ghabanbasani MZ, Spaepen M, Buyse I et al (1995) Increased and decreased relative risk for non-insulin-dependent diabetes mellitus conferred by HLA class II and by CD4 alleles. Clin Genet 47:225–230PubMed

27.

Vendrell J, Gutierrez C, Pastor R, Richart C (1995) A tumor necrosis factor-beta polymorphism associated with hypertriglyceridemia in non-insulin-dependent diabetes mellitus. Metabolism 44:691–694CrossRefPubMed

28.

Fernandez-Real JM, Gutierrez C, Ricart W et al (1997) The TNF-alpha gene Nco I polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels. Diabetes 46:1468–1472PubMed

29.

Fernandez-Real JM, Vendrell J, Ricart W et al (2000) Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients. Diabetes Care 23:831–837PubMed

30.

Fernandez-Real JM, Broch M, Vendrell J et al (2000) Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes 49:517–520PubMed

31.

Hoffstedt J, Andersson IL, Persson L, Isaksson B, Arner P (2002) The common −675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is strongly associated with obesity. Diabetologia 45:584–587CrossRefPubMed

32.

Perez-Luque E, Alaez C, Malacara JM et al (2003) Protective effect of DRB1 locus against type 2 diabetes mellitus in Mexican Mestizos. Hum Immunol 64:110–118CrossRefPubMed

33.

Wolford JK, Gruber JD, Ossowski VM et al (2003) A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab 78:136–144CrossRefPubMed

34.

Rosmond R, Chagnon M, Bouchard C, Bjorntorp P (2003) Increased abdominal obesity, insulin and glucose levels in nondiabetic subjects with a T29C polymorphism of the transforming growth factor-beta1 gene. Horm Res 59:191–194CrossRefPubMed

35.

Escobar-Morreale HF, Calvo RM, Villuendas G, Sancho J, San Millan JL (2003) Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism. Obes Res 11:987–996PubMed

36.

Illig T, Bongardt F, Schöpfer A et al (2004) Significant association of the interleukin-6 gene polymporphism C-174G and A-598G with type 2 diabetes. J Clin Endocrin Metab 89:5053–5058CrossRef

37.

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

38.

Dong ZM, Gutierrez-Ramos JC, Coxon A, Mayadas TN, Wagner DD (1997) A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci U S A 94:7526–7530CrossRefPubMed

39.

Wallenius V, Wallenius K, Ahren B et al (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79CrossRefPubMed

40.

Schafer K, Fujisawa K, Konstantinides S, Loskutoff DJ (2001) Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice. FASEB J 15:1840–1842PubMed

41.

Ma LJ, Mao SL, Taylor KL et al (2004) Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53:336–346PubMed

42.

Lijnen HR, Maquoi E, Morange P et al (2003) Nutritionally induced obesity is attenuated in transgenic mice overexpressing plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol 23:78–84CrossRefPubMed

43.

Perreault M, Marette A (2001) Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 7:1138–1143CrossRefPubMed

44.

Morange PE, Lijnen HR, Alessi MC, Kopp F, Collen D, Juhan-Vague I (2000) Influence of PAI-1 on adipose tissue growth and metabolic parameters in a murine model of diet-induced obesity. Arterioscler Thromb Vasc Biol 20:1150–1154PubMed

45.

Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed

46.

Goldstein BJ (2003) Insulin resistance: from benign to type 2 diabetis mellitus. Rev Cardiovasc Med 4 [Suppl 6]:S3–S10

47.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432CrossRefPubMed

48.

Bali D, Svetlanov A, Lee HW et al (1995) Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J Biol Chem 270:21464–21467CrossRefPubMed

49.

Terauchi Y, Sakura H, Yasuda K et al (1995) Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose. J Biol Chem 270:30253–30256CrossRefPubMed

50.

Grupe A, Hultgren B, Ryan A, Ma YH, Bauer M, Stewart TA (1995) Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell 83:69–78CrossRefPubMed

51.

Erickson JC, Clegg KE, Palmiter RD (1996) Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381:415–421CrossRefPubMed

52.

Erickson JC, Hollopeter G, Palmiter RD (1996) Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274:1704–1707CrossRefPubMed

53.

Janson J, Soeller WC, Roche PC et al (1996) Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci U S A 93:7283–7288CrossRefPubMed

54.

Stenbit AE, Tsao TS, Li J et al (1997) GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3:1096–1101CrossRefPubMed

55.

Bruning JC, Winnay J, Bonner-Weir S, Taylor SI, Accili D, Kahn CR (1997) Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88:561–572CrossRefPubMed

56.

Leiter EH (1997) Carboxypeptidase E and obesity in the mouse. J Endocrinol 155:211–214CrossRefPubMed

57.

Ren JM, Li PM, Zhang WR et al (1998) Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit profound defects in glucose homeostasis. Diabetes 47:493–497PubMed

58.

Withers DJ, Gutierrez JS, Towery H et al (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900–904CrossRefPubMed

59.

Masuzaki H, Paterson J, Shinyama H et al (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170CrossRefPubMed

60.

Kim JK, Fillmore JJ, Chen Y et al (2001) Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 98:7522–7527CrossRefPubMed

61.

Laustsen PG, Michael MD, Crute BE et al (2002) Lipoatrophic diabetes in Irs1(−/−)/Irs3(−/−) double knockout mice. Genes Dev 16:3213–3222CrossRefPubMed

62.

Hribal ML, Oriente F, Accili D (2002) Mouse models of insulin resistance. Am J Physiol Endocrinol Metab 282:E977–E981PubMed

63.

Mauvais-Jarvis F, Kulkarni RN, Kahn CR (2002) Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance. Clin Endocrinol (Oxf) 57:1–9CrossRef

64.

Hirosumi J, Tuncman G, Chang L et al (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336CrossRefPubMed

65.

Baudry A, Leroux L, Jackerott M, Joshi RL (2002) Genetic manipulation of insulin signaling, action and secretion in mice. Insights into glucose homeostasis and pathogenesis of type 2 diabetes. EMBO Rep 3:323–328CrossRefPubMed

66.

Valet P, Tavernier G, Castan-Laurell I, Saulnier-Blache JS, Langin D (2002) Understanding adipose tissue development from transgenic animal models. J Lipid Res 43:835–860PubMed

67.

Conarello SL, Li Z, Ronan J et al (2003) Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci U S A 100:6825–6830CrossRefPubMed

68.

Maedler K, Sergeev P, Ris F et al (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110:851–860CrossRefPubMed

69.

Shanmugam N, Reddy MA, Guha M, Natarajan R (2003) High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes 52:1256–1264PubMed

70.

Chen Y, Schneider DJ (2002) The independence of signaling pathways mediating increased expression of plasminogen activator inhibitor type 1 in HepG2 cells exposed to free fatty acids or triglycerides. Int J Exp Diabetes Res 3:109–118CrossRefPubMed

71.

Morohoshi M, Fujisawa K, Uchimura I, Numano F (1996) Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 45:954–959PubMed

72.

Morigi M, Angioletti S, Imberti B et al (1998) Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. J Clin Invest 101:1905–1915PubMed

73.

Guha M, Bai W, Nadler JL, Natarajan R (2000) Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem 275:17728–17739CrossRefPubMed

74.

Donath MY, Storling J, Maedler K, Mandrup-Poulsen T (2003) Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81:455–470CrossRefPubMed

75.

Weigert C, Brodbeck K, Staiger H et al (2004) Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor kappa B. J Biol Chem 279:23942–23952CrossRefPubMed

76.

Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2003) Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52:1–8PubMed

77.

Schiekofer S, Andrassy M, Chen J et al (2003) Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes 52:621–633PubMed

78.

Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed

79.

Hammes HP, Du X, Edelstein D et al (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299CrossRefPubMed

80.

Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142CrossRefPubMed

81.

Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671CrossRefPubMed

82.

Ceriello A, Falleti E, Motz E et al (1998) Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress. Horm Metab Res 30:146–149PubMed

83.

Esposito K, Nappo F, Marfella R et al (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106:2067–2072CrossRefPubMed

84.

Esposito K, Nappo F, Giugliano F et al (2003) Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am J Clin Nutr 78:1135–1140PubMed

85.

Krebs M, Geiger M, Polak K et al (2003) Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. Thromb Haemost 90:422–428PubMed

86.

Ceriello A, Quagliaro L, Piconi L et al (2004) Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 53:701–710PubMed

87.

van Oostrom AJ, van Dijk H, Verseyden C et al (2004) Addition of glucose to an oral fat load reduces postprandial free fatty acids and prevents the postprandial increase in complement component 3. Am J Clin Nutr 79:510–515PubMed

88.

Vlassara H, Palace MR (2002) Diabetes and advanced glycation endproducts. J Intern Med 251:87–101CrossRefPubMed

89.

Peppa M, Goldberg T, Cai W, Rayfield E, Vlassara H (2002) Glycotoxins: a missing link in the “relationship of dietary fat and meat intake in relation to risk of type 2 diabetes in men”. Diabetes Care 25:1898–1899PubMed

90.

Taylor R (2004) Causation of type 2 diabetes—the Gordian knot unravels. N Engl J Med 350:639–641CrossRefPubMed

91.

Arkan MC, Hevener AL, Greten FR et al (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198CrossRefPubMed

92.

Stumpo R, Kauer M, Martin S, Kolb H (2003) IL-10 induces gene expression in macrophages: partial overlap with IL-5 but not with IL-4 induced genes. Cytokine 24:46–56CrossRefPubMed

93.

Hanley AJ, Festa A, D’Agostino RB et al (2004) Metabolic and inflammation variable clusters and prediction of type 2 diabetes: factor analysis using directly measured insulin sensitivity. Diabetes 53:1773–1781PubMed

94.

Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830CrossRefPubMed

95.

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808CrossRefPubMed

96.

Fasshauer M, Klein J, Kralisch S et al (2004) Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 317:598–604CrossRefPubMed

97.

Chen W, Syldath U, Bellmann K, Burkart V, Kolb H (1999) Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol 162:3212–3219PubMed

98.

Ohashi K, Burkart V, Flohé S, Kolb H (2000) Heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558–561PubMed

99.

Ruan H, Lodish HF (2003) Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14:447–455CrossRefPubMed

100.

Senn JJ, Klover PJ, Nowak IA et al (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278:13740–13746CrossRefPubMed

101.

Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301CrossRefPubMed

102.

Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25:4–7CrossRefPubMed

103.

Peraldi P, Spiegelman B (1998) TNF-alpha and insulin resistance: summary and future prospects. Mol Cell Biochem 182:169–175CrossRefPubMed

104.

Rui L, Yuan M, Frantz D, Shoelson S, White MF (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 277:42394–42398CrossRefPubMed

105.

Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823PubMed

106.

Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14:561–566CrossRefPubMed

107.

Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859CrossRefPubMed

108.

Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556CrossRefPubMed

109.

Eskandari F, Webster JI, Sternberg EM (2003) Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 5:251–265CrossRefPubMed

110.

Pedersen BK, Steensberg A, Schjerling P (2001) Muscle-derived interleukin-6: possible biological effects. J Physiol 536:329–337CrossRefPubMed

111.

Penkowa M, Keller C, Keller P, Jauffred S, Pedersen BK (2003) Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise. FASEB J 17:2166–2168PubMed

112.

Tomiya A, Aizawa T, Nagatomi R, Sensui H, Kokubun S (2004) Myofibers express IL-6 after eccentric exercise. Am J Sports Med 32:503–508CrossRefPubMed

113.

Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK (2002) IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 283:E1272–E1278PubMed

114.

Steensberg A, van Hall G, Keller C et al (2002) Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation. J Physiol 541:273–281CrossRefPubMed

115.

Nybo L, Nielsen B, Pedersen BK, Moller K, Secher NH (2002) Interleukin-6 release from the human brain during prolonged exercise. J Physiol 542:991–995CrossRefPubMed

116.

Pedersen BK, Steensberg A, Fischer C et al (2003) Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil 24:113–119CrossRefPubMed

117.

van Hall G, Steensberg A, Sacchetti M et al (2003) Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 88:3005–3010CrossRefPubMed

118.

Steensberg A, Fischer CP, Sacchetti M et al (2003) Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol 548:631–638PubMed

119.

Kim HJ, Higashimori T, Park SY et al (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53:1060–1067PubMed

120.

Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO (2002) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565CrossRefPubMed

121.

Scheen AJ (2004) Pathophysiology of insulin secretion. Ann Endocrinol (Paris) 65:29–36

122.

Steppel JH, Horton ES (2004) Beta-cell failure in the pathogenesis of type 2 diabetes mellitus. Curr Diabetes Rep 4:169–175

123.

Zethelius B, Byberg L, Hales CN, Lithell H, Berne C (2003) Proinsulin and acute insulin response independently predict type 2 diabetes mellitus in men—report from 27 years of follow-up study. Diabetologia 46:20–26PubMed

124.

Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG (2001) Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50:1771–1777PubMed

125.

Carlsson C, Borg LA, Welsh N (1999) Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro. Endocrinology 140:3422–3428CrossRefPubMed

126.

Maedler K, Spinas GA, Lehmann R et al (2001) Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes 50:1683–1690PubMed

127.

Robertson RP, Harmon J, Tran PO, Poitout V (2004) Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 53 [Suppl 1]:S119–S124PubMed

128.

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110PubMed

129.

Deng S, Vatamaniuk M, Huang X et al (2004) Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 53:624–632PubMed

130.

Jansson L, Eizirik DL, Pipeleers DG, Borg LA, Hellerstrom C, Andersson A (1995) Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice. J Clin Invest 96:721–726PubMed

131.

Eizirik DL, Jansson L, Flodstrom M, Hellerstrom C, Andersson A (1997) Mechanisms of defective glucose-induced insulin release in human pancreatic islets transplanted to diabetic nude mice. J Clin Endocrinol Metab 82:2660–2663CrossRefPubMed

132.

Moriwaki M, Itoh N, Miyagawa J et al (1999) Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset type I diabetes mellitus. Diabetologia 42:1332–1340CrossRefPubMed

133.

Mandrup-Poulsen T (1996) The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 39:1005–1029PubMed

134.

Eizirik DL, Mandrup-Poulsen T (2001) A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133CrossRefPubMed

135.

Maedler K, Sergeev P, Ehses JA et al (2004) Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc Natl Acad Sci U S A 101:8138–8143CrossRefPubMed

136.

Maedler K, Fontana A, Ris F et al (2002) FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc Natl Acad Sci U S A 99:8236–8241CrossRefPubMed

137.

Maedler K, Storling J, Sturis J et al (2004) Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. Diabetes 53:1706–1713PubMed

138.

Maestre I, Jordan J, Calvo S et al (2003) Mitochondrial dysfunction is involved in apoptosis induced by serum withdrawal and fatty acids in the beta-cell line INS-1. Endocrinology 144:335–345CrossRefPubMed

139.

Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia 45:85–96CrossRefPubMed

140.

Koshkin V, Wang X, Scherer PE, Chan CB, Wheeler MB (2003) Mitochondrial functional state in clonal pancreatic beta-cells exposed to free fatty acids. J Biol Chem 278:19709–19715CrossRefPubMed

141.

Schrauwen P, Hesselink MK (2004) Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 53:1412–1417PubMed

142.

Lupi R, Dotta F, Marselli L et al (2002) Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 51:1437–1442PubMed

143.

Aarnes M, Schonberg S, Grill V (2002) Fatty acids potentiate interleukin-1beta toxicity in the beta-cell line INS-1E. Biochem Biophys Res Commun 296:189–193CrossRefPubMed

144.

Srinivasan S, Bolick DT, Hatley ME et al (2004) Glucose regulates interleukin-8 production in aortic endothelial cells through activation of the p38 MAP kinase pathway in diabetes. J Biol Chem 279:31930–31936CrossRefPubMed

145.

Altannavch TS, Roubalova K, Kucera P, Andel M (2004) Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation. Physiol Res 53:77–82PubMed

146.

Takaishi H, Taniguchi T, Takahashi A, Ishikawa Y, Yokoyama M (2003) High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem Biophys Res Commun 305:122–128CrossRefPubMed

147.

Asakawa H, Miyagawa J, Hanafusa T, Kuwajima M, Matsuzawa Y (1997) High glucose and hyperosmolarity increase secretion of interleukin-1 beta in cultured human aortic endothelial cells. J Diabetes Complicat 11:176–179CrossRefPubMed

148.

Kharroubi I, Ladriere L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DL (2004) Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology 145:5087–5096CrossRefPubMed

149.

Todaro M, Di Gaudio F, Lavitrano M, Stassi G, Papaccio G (2003) Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation. Endocrinology 144:4264–4271CrossRefPubMed

150.

Gallucci S, Matzinger P (2001) Danger signals: SOS to the immune system. Curr Opin Immunol 13:114–119CrossRefPubMed

151.

Lipscomb MF, Masten BJ (2002) Dendritic cells: immune regulators in health and disease. Physiol Rev 82:97–130PubMed

152.

Pittoni V, Valesini G (2002) The clearance of apoptotic cells: implications for autoimmunity. Autoimmun Rev 1:154–161CrossRefPubMed

153.

Wick G, Perschinka H, Millonig G (2001) Atherosclerosis as an autoimmune disease: an update. Trends Immunol 22:665–669CrossRefPubMed

154.

Frostegard J (2002) Autoimmunity, oxidized LDL and cardiovascular disease. Autoimmun Rev 1:233–237CrossRefPubMed

155.

George J, Yacov N, Breitbart E et al (2004) Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I. Cardiovasc Res 62:603–609CrossRefPubMed

156.

Clark A, Wells CA, Buley ID et al (1988) Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 9:151–159PubMed

157.

Hayden MR (2002) Islet amyloid, metabolic syndrome, and the natural progressive history of type 2 diabetes mellitus. JOP 3:126–138PubMed

158.

Yoon KH, Ko SH, Cho JH et al (2003) Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–2308CrossRefPubMed

159.

de Koning EJ, van den Brand JJ, Mott VL et al (1998) Macrophages and pancreatic islet amyloidosis. Amyloid 5:247–254PubMed

160.

Kubaszek A, Pihlajamaki J, Komarovski V et al (2003) Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 52:1872–1876PubMed

161.

Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91PubMed

162.

Paquot N, Castillo MJ, Lefebvre PJ, Scheen AJ (2000) No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 85:1316–1319CrossRefPubMed

163.

Di Rocco P, Manco M, Rosa G, Greco AV, Mingrone G (2004) Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab. Obes Res 12:734–739PubMed

164.

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

165.

Rask-Madsen C, Dominguez H, Ihlemann N, Hermann T, Kober L, Torp-Pedersen C (2003) Tumor necrosis factor-alpha inhibits insulin’s stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 108:1815–1821CrossRefPubMed

166.

Shoelson SE, Lee J, Yuan M (2003) Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27 [Suppl 3]:S49–S52CrossRefPubMed

167.

Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109:II2–II10PubMed

168.

Zheng Z, Lee JE, Yenari MA (2003) Stroke: molecular mechanisms and potential targets for treatment. Curr Mol Med 3:361–372CrossRefPubMed

169.

Casserly I, Topol E (2004) Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet 363:1139–1146CrossRefPubMed

170.

Franceschi C, Bonafe M (2003) Centenarians as a model for healthy aging. Biochem Soc Trans 31:457–461CrossRefPubMed

171.

Grimble RF (2003) Inflammatory response in the elderly. Curr Opin Clin Nutr Metab Care 6:21–29CrossRefPubMed

172.

Yucesoy B, Kashon ML, Luster MI (2003) Cytokine polymorphisms in chronic inflammatory diseases with reference to occupational diseases. Curr Mol Med 3:39–48CrossRefPubMed

173.

McGeer PL, McGeer EG (2001) Polymorphisms in inflammatory genes and the risk of Alzheimer disease. Arch Neurol 58:1790–1792CrossRefPubMed

174.

Duchen MR (2004) Roles of mitochondria in health and disease. Diabetes 53 [Suppl 1]:S96–S102PubMed

175.

McCord JM (2002) Superoxide dismutase in aging and disease: an overview. Methods Enzymol 349:331–341PubMed

176.

Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53 [Suppl 3]:S26–S36CrossRefPubMed

177.

Yoshida M (2003) Potential role of statins in inflammation and atherosclerosis. J Atheroscler Thromb 10:140–144PubMed

178.

Santangelo F (2003) Intracellular thiol concentration modulating inflammatory response: influence on the regulation of cell functions through cysteine prodrug approach. Curr Med Chem 10:2599–2610CrossRefPubMed

179.

Rosenson RS (2004) Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis 173:1–12CrossRefPubMed

180.

Violi F, Loffredo L, Musella L, Marcoccia A (2004) Should antioxidant status be considered in interventional trials with antioxidants? Heart 90:598–602CrossRefPubMed

181.

Cuzzocrea S, Thiemermann C, Salvemini D (2004) Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr Med Chem 11:1147–1162PubMed

182.

Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53 [Suppl 1]:S110–S118PubMed

183.

Schmidt MI, Duncan BB (2003) Diabesity: an inflammatory metabolic condition. Clin Chem Lab Med 41:1120–1130CrossRefPubMed

184.

Theuma P, Fonseca VA (2003) Inflammation and emerging risk factors in diabetes mellitus and atherosclerosis. Curr Diabetes Rep 3:248–254

185.

Garg R, Tripathy D, Dandona P (2003) Insulin resistance as a proinflammatory state: mechanisms, mediators, and therapeutic interventions. Curr Drug Targets 4:487–492CrossRefPubMed

186.

Haffner SM (2003) Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol 92:18J–26JCrossRefPubMed

187.

Aldhahi W, Hamdy O (2003) Adipokines, inflammation, and the endothelium in diabetes. Curr Diabetes Rep 3:293–298

188.

Yudkin JS, Panahloo A, Stehouwer C et al (2000) The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in type II diabetic subjects. Diabetologia 43:1099–1106CrossRefPubMed

189.

Sattar N, Gaw A, Scherbakova O et al (2003) Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 108:414–419CrossRefPubMed

190.

Milani RV, Lavie CJ, Mehra MR (2004) Reduction in C-reactive protein through cardiac rehabilitation and exercise training. J Am Coll Cardiol 43:1056–1061CrossRefPubMed

191.

Clifton PM, Noakes M, Keogh J, Foster P (2003) How effective are meal replacements for treating obesity? Asia Pac J Clin Nutr 12 [Suppl]:S51

192.

Brinkworth GD, Noakes M, Keogh JB, Luscombe ND, Wittert GA, Clifton PM (2004) Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord 28:661–670CrossRefPubMed

193.

Marfella R, Esposito K, Siniscalchi M et al (2004) Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care 27:47–52PubMed

194.

Clifton PM (2003) Diet and C-reactive protein. Curr Atheroscler Rep 5:431–436PubMed

195.

Kopp HP, Kopp CW, Festa A et al (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23:1042–1047CrossRefPubMed

196.

Esposito K, Pontillo A, Di Palo C et al (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804CrossRefPubMed

197.

Hanusch-Enserer U, Cauza E, Spak M et al (2003) Acute-phase response and immunological markers in morbid obese patients and patients following adjustable gastric banding. Int J Obes Relat Metab Disord 27:355–361CrossRefPubMed

198.

Laimer M, Ebenbichler CF, Kaser S et al (2002) Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention. Int J Obes Relat Metab Disord 26:659–662CrossRefPubMed

199.

Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET (2002) Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 105:564–569CrossRefPubMed

200.

Esposito K, Pontillo A, Ciotola M et al (2002) Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab 87:3864–3866CrossRefPubMed

201.

Heilbronn LK, Noakes M, Clifton PM (2001) Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women. Arterioscler Thromb Vasc Biol 21:968–970PubMed

202.

Bastard JP, Jardel C, Bruckert E, Vidal H, Hainque B (2000) Variations in plasma soluble tumour necrosis factor receptors after diet-induced weight loss in obesity. Diabetes Obes Metab 2:323–325CrossRefPubMed

203.

Straczkowski M, Kowalska I, Dzienis-Straczkowska S et al (2001) Changes in tumor necrosis factor-alpha system and insulin sensitivity during an exercise training program in obese women with normal and impaired glucose tolerance. Eur J Endocrinol 145:273–280CrossRefPubMed

204.

Ziccardi P, Nappo F, Giugliano G et al (2002) Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105:804–809CrossRefPubMed

205.

Bruun JM, Verdich C, Toubro S, Astrup A, Richelsen B (2003) Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men. Eur J Endocrinol 148:535–542CrossRefPubMed

206.

Bastard JP, Jardel C, Bruckert E et al (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85:3338–3342CrossRefPubMed

207.

Troseid M, Lappegard KT, Claudi T et al (2004) Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur Heart J 25:349–355CrossRefPubMed

208.

Fukuzawa M, Satoh J, Qiang X et al (1999) Inhibition of tumor necrosis factor-alpha with anti-diabetic agents. Diabetes Res Clin Pract 43:147–154CrossRefPubMed

209.

Akbar DH (2003) Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome. Endocrine 20:215–218CrossRefPubMed

210.

Chu NV, Kong AP, Kim DD et al (2002) Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care 25:542–549PubMed

211.

Carlsen SM, Waage A, Grill V, Folling I (1998) Metformin increases circulating tumour necrosis factor-alpha levels in non-obese non-diabetic patients with coronary heart disease. Cytokine 10:66–69CrossRefPubMed

212.

Ebeling P, Teppo AM, Koistinen HA et al (1999) Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with type II diabetes. Diabetologia 42:1433–1438CrossRefPubMed

213.

Varo N, Vicent D, Libby P et al (2003) Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients: a novel target of thiazolidinediones. Circulation 107:2664–2669CrossRefPubMed

214.

Katsuki A, Sumida Y, Murata K et al (2000) Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes. Diabetes Obes Metab 2:189–191CrossRefPubMed

215.

Jeschke MG, Einspanier R, Klein D, Jauch KW (2002) Insulin attenuates the systemic inflammatory response to thermal trauma. Mol Med 8:443–450PubMed

216.

Dandona P, Aljada A, Mohanty P (2002) The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 45:924–930CrossRefPubMed

217.

Dandona P, Aljada A, Mohanty P et al (2001) Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab 86:3257–3265CrossRefPubMed

218.

Muller S, Martin S, Koenig W et al (2002) Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 45:805–812CrossRefPubMed

Titel: An immune origin of type 2 diabetes?
verfasst von: H. Kolb
T. Mandrup-Poulsen
Publikationsdatum: 01.06.2005
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 6/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-005-1764-9

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