Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta

Article Article scientifique Article Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta eng 2004 author Zeender Eve Salome 105073 author Maedler K. author Bosco Domenico 23285 author Berney Thierry 63319 author Donath Michel 71965 author Halban Philippe A. 25597 5059-5066 10.1210/jc.2004-0446 15472206 0021-972X http://jcem.endojournals.org/cgi/reprint/89/10/5059.pdf Decreased functional beta-cell mass in type 1 and type 2 diabetes is due to beta-cell apoptosis and impaired secretory function suggested to be mediated, in part, by immune- and/or high-glucose-induced production of IL-1beta acting through the nuclear factor kappaB (NFkappaB)/Fas pathway. The aim of this study was to determine whether two drugs believed to block NFkappaB activation, the thiazolidinedione (glitazone) pioglitazone and the nonsteroidal antiinflammatory drug sodium salicylate, can protect human beta-cells against the toxic effects of IL-1beta and high glucose in vitro. Human islets were maintained in culture 2-4 d at 100 mg/dl (5.5 mm) glucose with or without (control) IL-1beta or at 600 mg/dl (33.3 mm) glucose. IL-1beta and 600 mg/dl glucose increased beta-cell apoptosis and abolished short-term glucose-stimulated insulin secretion. Both drugs protected partially against loss of glucose-stimulated insulin secretion and prevented completely increased apoptosis caused by IL-1beta or 600 mg/dl glucose. IL-1beta secretion from islets was increased by 4-d culture at 600 mg/dl, and this was blocked by pioglitazone. Both drugs prevented activation of beta-cell NFkappaB by high glucose. Pioglitazone and sodium salicylate thus protect human islets against the detrimental effects of IL-1beta and high glucose by blocking NFkappaB activation and may therefore be useful in retarding the manifestation and progression of diabetes. Anti-Inflammatory Agents, Non-Steroidal/ pharmacology Apoptosis/ drug effects Cells, Cultured Glucose/pharmacology Humans Hypoglycemic Agents/ pharmacology Insulin/metabolism/secretion Interleukin-1/pharmacology/secretion Islets of Langerhans/cytology/ drug effects/metabolism NF-kappa B/metabolism Nitric Oxide/metabolism Sodium Salicylate/ pharmacology Thiazolidinediones/ pharmacology Dewey 616 Dewey 617 Dewey 576.5 135 Département de médecine génétique et développement 21D 56 Département de médecine 221 57 Département de chirurgie 222 false 246 Fonction de l'îlot de Langerhans 324 357 La transplantation d'îlots de Langerhans 623 The Journal of clinical endocrinology and metabolism 89 10 92f93f4c-5631-4985-b9dd-fa085f1ef741 Article Restricted file1.pdf 275744 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta	The Journal of clinical endocrinology and metabolism			2004	618	0

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Donath, Michel