Pancreatic islet inflammation in type 2 diabetes: From α and β cell compensation to dysfunction

References

• Akirav E, Kushner JA, Herold KC. (2008). Beta-cell mass and type 1 diabetes: going, going, gone? Diabetes 57:2883–8.
   PubMedGoogle Scholar
• Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M. (2005). IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191–8.
   PubMed Web of Science ®Google Scholar
• Boni-Schnetzler M, Thorne J, Parnaud G, Marselli L, Ehses JA, Kerr-Conte J, Pattou F, Halban PA, Weir GC, Donath MY. (2008). Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta-cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab 93:4065–74.
   PubMed Web of Science ®Google Scholar
• Bonner-Weir S. (2000). Islet growth and development in the adult. J Mol Endocrinol 24:297–302.
   PubMed Web of Science ®Google Scholar
• Butler PC, Meier JJ, Butler AE, Bhushan A. (2007). The replication of beta cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab 3:758–68.
   PubMedGoogle Scholar
• Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. (2005). Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11:183–90.
   PubMed Web of Science ®Google Scholar
• Campbell IL, Cutri A, Wilson A, Harrison, LC. (1989). Evidence for IL-6 production by and effects on the pancreatic beta-cell. J Immunol 143:1188–91.
   PubMed Web of Science ®Google Scholar
• Campbell IL, Hobbs MV, Dockter J, Oldstone MB, Allison J. (1994). Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice. Am J Pathol 145:157–66.
   PubMed Web of Science ®Google Scholar
• Campbell IL, Kay TWH, Oxbrow L, Harrison LC. (1991). Essential role for interferon and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87:739–42.
   PubMed Web of Science ®Google Scholar
• Cardozo AK, Proost P, Gysemans C, Chen MC, Mathieu C, Eizirik DL. (2003). IL-1beta and IFN-gamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia 46:255–66.
   PubMed Web of Science ®Google Scholar
• Chen MC, Schuit F, Eizirik DL. (1999). Identification of IL-1beta-induced messenger RNAs in rat pancreatic beta cells by differential display of messenger RNA. Diabetologia 42:1199–203.
   PubMed Web of Science ®Google Scholar
• Deng S, Vatamaniuk M, Huang X, Doliba N, Lian MM, Frank A, Velidedeoglu E, Desai NM, Koeberlein B, Wolf B. et al. (2004). Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 53:624–32.
   PubMed Web of Science ®Google Scholar
• Di Gregorio GB, Hensley L, Lu T, Ranganathan G, Kern PA. (2004). Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab 287:E182–7.
   PubMed Web of Science ®Google Scholar
• DiCosmo BF, Picarella D, Flavell RA. (1994). Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice. Int Immunol 6:1829–37.
   PubMed Web of Science ®Google Scholar
• Dinarello CA. (1996). Biologic basis for interleukin-1 in disease. Blood 87:2095–147.
   PubMed Web of Science ®Google Scholar
• Dinarello CA. (2007). A signal for the caspase-1 inflammasome free of TLR. Immunity 26:383–5.
   PubMed Web of Science ®Google Scholar
• Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Rütti S, Perren A, Böni-Schnetzler M, Ehses JA. (2008a). Islet inflammation in type 2 diabetes: From metabolic stress to therapy. Diabetes Care Rev; 31 Supp 2:S161–4.
   Google Scholar
• Donath MY, Weder C, Whitmore J, Bauer RJ, Der K, Scannon PJ, Dinarello C, Solinger AM. (2008b). XOMA 052, an anti-IL-1beta antibody, in a double-blind, placebo-controlled, dose escalation study of the safety and pharmacokinetics in patients with type 2 diabets mellitus – a new approach to therapy. Diabetologia 51:S7.
   Web of Science ®Google Scholar
• Ehses JA, Calderari S, Irminger JC, Serradas P, Giroix MH, Egli A, Portha B, Donath MY, Homo-Delarche F. (2007a). Islet inflammation in type 2 diabetes (T2D): From endothelial to beta-cell dysfunction. Current Immunol Rev 3:216–32.
   Google Scholar
• Ehses JA, Lacraz G, Giroix MH, Schmidlin F, Coulaud J, Kassis N, Irminger JC, Kergoat M, Portha B, Homo-Delarche F and Donath MY. (Forthcoming). IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Natl Acad Sci USA.
   Web of Science ®Google Scholar
• Ehses JA, Perren A, Eppler E, Ribaux P, Pospisilik JA, Maor-Cahn R, Gueripel X, Ellingsgaard H, Schneider MK, Biollaz G. et al. (2007b). Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–70.
   PubMed Web of Science ®Google Scholar
• Eizirik DL, Sandler S, Welsh N, Cetkovic-Cvrlje M, Nieman A, Geller DA, Pipeleers DG, Bendtzen K, Hellerstrom C. (1994). Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J Clin Invest 93;1968–74.
   PubMed Web of Science ®Google Scholar
• Ellingsgaard H, Ehses JA, Hammar E, Van Lommel L, Quintens R, Martens G, Kerr-Conte J, Pattou F, Berney T, Pipeleers D. et al. (2008). Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc Natl Acad Sci USA 105:13163–8.
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Muscelli E, Natali A, Gabriel, R, Mitrakou, A, Flyvbjerg A, Golay A, Hojlund K. (2007). Association of fasting glucagon and proinsulin concentrations with insulin resistance. Diabetologia 50:2342–7.
   PubMed Web of Science ®Google Scholar
• Guilherme A, Virbasius JV, Puri V, Czech MP. (2008). Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 9:367–77.
   PubMed Web of Science ®Google Scholar
• Haataja L, Gurlo T, Huang CJ, Butler PC. (2008). Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev 29:303–16.
   PubMed Web of Science ®Google Scholar
• Halban PA. (2008). Cell therapy for type 2 diabetes: Is it desirable and can we get it? Diabetes Obes Metab 10 Suppl 4:205–11.
   PubMedGoogle Scholar
• Hammar E, Parnaud G, Bosco D, Perriraz N, Maedler K, Donath M, Rouiller DG, Halban PA. (2004). Extracellular matrix protects pancreatic beta-cells against apoptosis: role of short- and long-term signaling pathways. Diabetes 53:2034–41.
   PubMed Web of Science ®Google Scholar
• Hammar EB, Irminger JC, Rickenbach K, Parnaud G, Ribaux P, Bosco D, Rouiller DG, Halban PA. (2005). Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. J Biol Chem 280:30630–37.
   PubMed Web of Science ®Google Scholar
• Herder C, Haastert B, Muller-Scholze S, Koenig W, Thorand B, Holle R, Wichmann HE, Scherbaum WA, Martin S, Kolb H. (2005). Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: Results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes 54 Suppl 2:S11–17.
   PubMedGoogle Scholar
• Homo-Delarche F, Calderari S, Irminger JC, Gangnerau MN, Coulaud J, Rickenbach K, Dolz M, Halban P, Portha B, Serradas P. (2006). Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes, the GK rat. Diabetes 55:1625–33.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS, Erbay E. (2008). Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8:923–34.
   PubMed Web of Science ®Google Scholar
• Hull RL, Westermark GT, Westermark P, Kahn SE. (2004). Islet amyloid: A critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab 89:3629–43.
   PubMed Web of Science ®Google Scholar
• Huypens P, Ling Z, Pipeleers D, Schuit F. (2000). Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Diabetologia 43:1012–19.
   PubMed Web of Science ®Google Scholar
• Jacobsen ML, Ronn SG, Bruun C, Larsen CM, Eizirik DL, Mandrup-Poulsen T, Billestrup N. (2009). IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells. Diabetologia 52:281–8.
   PubMed Web of Science ®Google Scholar
• Kahn SE, Andrikopoulos S, Verchere, CB. (1999). Islet amyloid: A long-recognized but underappreciated pathological feature of type 2 diabetes. Diabetes 48:241–53.
   PubMed Web of Science ®Google Scholar
• Kahn SE, Hull RL, Utzschneider KM. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–46.
   PubMed Web of Science ®Google Scholar
• Kamimura D, Ishihara K, Hirano T. (2003). IL-6 signal transduction and its physiological roles: The signal orchestration model. Rev Physiol Biochem Pharmacol 149:1–38.
   PubMed Web of Science ®Google Scholar
• Kim JW, Ko SH, Cho JH, Sun C, Hong OK, Lee SH, Kim JH, Lee KW, Kwon HS, Lee JM. et al. (2008). Loss of beta-cells with fibrotic islet destruction in type 2 diabetes mellitus. Front Biosci 13:6022–33.
   Google Scholar
• Kishimoto T. (1989). The biology of interleukin-6. Blood 74:1–10.
   PubMed Web of Science ®Google Scholar
• Kristiansen OP, Mandrup-Poulsen T. (2005). Interleukin-6 and diabetes: The good, the bad, or the indifferent? Diabetes 54 Suppl 2:S114–24.
   PubMed Web of Science ®Google Scholar
• Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. (2007). Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356:1517–26.
   PubMed Web of Science ®Google Scholar
• Li X, Zhang L, Meshinchi S, Dias-Leme C, Raffin D, Johnson JD, Treutelaar MK, Burant CF. (2006). Islet microvasculature in islet hyperplasia and failure in a model of type 2 diabetes. Diabetes 55:2965–73.
   PubMed Web of Science ®Google Scholar
• Maedler K, Schulthess FT, Bielman C, Berney T, Bonny C, Prentki M, Donath MY, Roduit R. (2008). Glucose and leptin induce apoptosis in human beta-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases. Faseb J 22:1905–13.
   PubMed Web of Science ®Google Scholar
• Maedler K, Schumann DM, Sauter N, Ellingsgaard H, Bosco D, Baertschiger R, Iwakura Y, Oberholzer J, Wollheim CB, Gauthier BR, Donath MY. (2006). Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. Diabetes 55:2713–22.
   PubMed Web of Science ®Google Scholar
• Maedler K, Sergeev P, Ehses JA, Mathe Z, Bosco D, Berney T, Dayer JM, Reinecke M, Halban PA, Donath MY. (2004). Leptin modulates beta-cell expression of the IL-1 receptor antagonist and release of IL-1beta in human islets. Proc Nat Acad Sci USA 101:8138–43.
   PubMed Web of Science ®Google Scholar
• Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY. (2002). Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110:851–60.
   PubMed Web of Science ®Google Scholar
• Marselli L, Sgroi DC, Thorne J, Dahiya S, Torri S, Omer A, Del Prato S, Towia L, Otu HH, Sharma A. et al. (2007). Evidence of inflammatory markers in beta cells of type 2 diabetic subjects. Diabetologia 50:S178.
   PubMed Web of Science ®Google Scholar
• McCarthy MI, Hattersley AT. (2008). Learning from molecular genetics: Novel insights arising from the definition of genes for monogenic and type 2 diabetes. Diabetes 57:2889–98.
   PubMed Web of Science ®Google Scholar
• Mooney RA. (2007). Counterpoint: Interleukin-6 does not have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 102:816–18; discussion 818–19.
   PubMed Web of Science ®Google Scholar
• Odegaard JI, Chawla A. (2008). Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract Endocrinol Metab 4:619–26.
   PubMedGoogle Scholar
• Osborn O, Brownell SE, Sanchez-Alavez M, Salomon D, Gram H, Bartfai T. (2008). Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity. Cytokine 44:141–8.
   PubMed Web of Science ®Google Scholar
• Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG. (2008). Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 8:301–9.
   PubMed Web of Science ®Google Scholar
• Pedersen BK, Febbraio MA. (2007). Point: Interleukin-6 does have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 102:814–16.
   PubMed Web of Science ®Google Scholar
• Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Wolsk-Petersen E, Febbraio M. (2004). The metabolic role of IL-6 produced during exercise: Is IL-6 an exercise factor? Proc Nutr Soc 63:263–67.
   PubMed Web of Science ®Google Scholar
• Portha B, Lacraz G, Kergoat M, Homo-Delarche F, Giroix MH, Bailbe D, Gangnerau MN, Dolz M, Tourrel-Cuzin C, Movassat J. (2009). The GK rat beta-cell: A prototype for the diseased human beta-cell in type 2 diabetes? Mol Cell Endocrinol 297:73–85.
   PubMed Web of Science ®Google Scholar
• Poupart P, Vandenabeele P, Cayphas S, Van Snick J, Haegeman G, Kruys V, Fiers W, Content J. (1987). B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-beta 2, HPGF). Embo J 6:1219–24.
   PubMed Web of Science ®Google Scholar
• Prentki M, Nolan CJ. (2006). Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802–12.
   PubMed Web of Science ®Google Scholar
• Rahier J, Goebbels RM, Henquin JC. (1983). Cellular composition of the human diabetic pancreas. Diabetologia 24, 366–71.
   PubMed Web of Science ®Google Scholar
• Rhodes CJ. (2005). Type 2 diabetes – a matter of beta-cell life and death? Science 307:380–84.
   PubMed Web of Science ®Google Scholar
• Ribaux P, Ehses JA, Lin-Marq N, Carrozzino F, Boni-Schnetzler M, Hammar E, Irminger JC, Donath M, Halban PA. (2007). Induction of CXCL1 by extracellular matrix and autocrine enhancement by IL-1 in rat pancreatic {beta}-cells. Endocrinology 148:5582–90.
   PubMed Web of Science ®Google Scholar
• Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. (2009). Islet-associated macrophages in type 2 diabetes. Diabetologia 6: Epub ahead of print.
   Google Scholar
• Sabio G, Das M, Mora A, Zhang Z, Jun JY, Ko HJ, Barrett T, Kim JK, Davis RJ. (2008). A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science 322:1539–43.
   PubMed Web of Science ®Google Scholar
• Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. (2008). The anti-inflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia. Endocrinology 149, 2208–18.
   PubMed Web of Science ®Google Scholar
• Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ. et al. (2007). Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–6.
   PubMed Web of Science ®Google Scholar
• Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU. et al. (2007). A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–5.
   PubMed Web of Science ®Google Scholar
• Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S. et al. (2007). A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–5.
   PubMed Web of Science ®Google Scholar
• Sorense, H, Winzell MS, Brand CL, Fosgerau K, Gelling RW, Nishimura E, Ahren B. (2006). Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function. Diabetes 55:3463–9.
   PubMed Web of Science ®Google Scholar
• Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. (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 52:812–17.
   PubMed Web of Science ®Google Scholar
• Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S. et al. (2007). A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39;770–75.
   PubMed Web of Science ®Google Scholar
• Strissel KJ, Stancheva Z, Miyoshi H, Perfield 2nd JW, DeFuria J, Jick Z, Greenberg A.S, Obin MS. (2007). Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56:2910–18.
   PubMed Web of Science ®Google Scholar
• Tessem JS, Jensen JN, Pelli H, Dai XM, Zong XH, Stanley ER, Jensen J, DeGregori J. (2008). Critical roles for macrophages in islet angiogenesis and maintenance during pancreatic degeneration. Diabetes 57:1605–17.
   PubMed Web of Science ®Google Scholar
• Unger RH, Orci L. (1975). The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1, 14–16.
   PubMed Web of Science ®Google Scholar
• Wadt KA, Larsen CM, Andersen HU, Nielsen K, Karlsen AE, Mandrup-Poulsen T. (1998). Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. Diabetes 47:1602–8.
   PubMedGoogle Scholar
• Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. (2002). Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–9.
   PubMed Web of Science ®Google Scholar
• Weir GC, Bonner-Weir S. (2004). Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 53 Suppl 3:S16–21.
   PubMed Web of Science ®Google Scholar
• Weksler-Zangen S, Raz I, Lenzen S, Jorns A, Ehrenfeld S, Amir G, Oprescu A, Yagil Y, Yagil C, Zangen DH, Kaiser N. (2008). Impaired glucose-stimulated insulin secretion is coupled with exocrine pancreatic lesions in the Cohen diabetic rat. Diabetes 57:279–87.
   PubMed Web of Science ®Google Scholar
• Welsh N, Cnop M, Kharroubi I, Bugliani M, Lupi R, Marchetti P, Eizirik DL. (2005). Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? Diabetes 54:3238–44.
   PubMed Web of Science ®Google Scholar
• Wideman RD, Yu IL, Webber TD, Verchere CB, Johnson JD, Cheung AT, Kieffer TJ. (2006). Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1). Proc Natl Acad Sci USA 103:13468–73.
   PubMed Web of Science ®Google Scholar
• Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha BY, Lee KW. et al. (2003). Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–8.
   PubMed Web of Science ®Google Scholar
• Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM. et al. (2007). Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–41.
   PubMed Web of Science ®Google Scholar
• Zimmet P, Alberti KG, Shaw J. (2001). Global and societal implications of the diabetes epidemic. Nature 414;782–7.
   PubMed Web of Science ®Google Scholar
• Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J. (2005). The metabolic syndrome: A global public health problem and a new definition. J Atheroscler Thromb 12:295–300.
   PubMed Web of Science ®Google Scholar