ArrayExpress Uploader0mousedistilled water for 21 dayswild typedistilled water for 21 dayswild typedistilled water containing 2mg/dl of sodium tungstate for 21 dayswild typedistilled water containing 2mg/dl of sodium tungstate for 21 dayswild typedistilled water for 21 daysIrs2 knockout (Irs2 -/-)distilled water for 21 daysIrs2 knockout (Irs2 -/-)distilled water containing 2mg/dl of sodium tungstate for 21 daysIrs2 knockout (Irs2 -/-)distilled water containing 2mg/dl of sodium tungstate for 21 daysIrs2 knockout (Irs2 -/-)7136arrayexpress_sid6Relative beta cell deficit and increased beta cell apoptosis are hallmarks of type 2 diabetes (T2D). The Insulin/Insulin Growth Factor...E-GEOD-43620/profile/8773/arrayexpressuploader28basalbeta cellbodycellcentralgenomeglucoseinsulinDec.12, 2014Falseeffects-of-sodium-tungstate-administration-in-irs2E-GEOD-43620_A-AFFY-45Effects of sodium tungstate administration in Irs2 -/- miceNov.12, 2014Relative beta cell deficit and increased beta cell apoptosis are hallmarks of type 2 diabetes (T2D). The Insulin/Insulin Growth Factor (Igf) signaling pathway is an established regulator of beta cell survival and is found downregulated in human T2D islets. The Insulin Receptor Substrate 2 (Irs2) plays a central role in the coordination of this pathway in beta cells. Thus, Irs2 knockout mice (Irs2 -/-) exhibit increased beta cell apoptosis that leads to a progressive decline of beta cell mass and hyperglycaemia. In this study, we sought to determine whether the anti-diabetic compound sodium tungstate could prevent the onset of diabetes in Irs2 -/- mice. Oral administration of tungstate resulted in an overall improvement in whole-body glucose tolerance in Irs2 -/- mice which correlated with increased beta cell mass. Enhanced beta cell mass was due to a dramatic reduction of beta cell apoptosis without changes in proliferation. Whole genome gene profiling analysis of islets isolated from treated Irs2 -/- mice confirmed a broad impact of tungstate on cell death pathways. Mechanistically, tungstate induced Erk1/2 phosphorylation in islets in vitro and, in agreement, treated Irs2 -/- islets exhibited increased basal Erk1/2 phosphorylation. Tungstate also downregulated expression of apoptosis-related genes in Irs2-/- islets in vitro, uncovering a direct effect of this compound in islets. All together, our data demonstrate that tungstate can restore beta cell mass and glucose homeostasis in a context of deficient Insulin/Igf signaling. This study underscores the importance of developing strategies specifically designed to arrest beta cell apoptosis as a means to prevent progressive beta cell failure in diabetes. 10-week old WT and Irs2 -/- mice were randomly divided into two treatment group, in a total of 4 experimental groups. For 21 days one group received distilled water as drinking water (untreated group) whilst the other received ad libitum a solution of 2mg/ml of sodium tungstate in distilled water (treated group). For each experimental group 2 independent samples were analysed, in a total of 8 samples.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43620http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43620/samples/