{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM1067240": {"DRINKING WATER": "distilled water for 21 days", "GENOTYPE": "wild type"}}, {"GSM1067240": {"DRINKING WATER": "distilled water for 21 days", "GENOTYPE": "wild type"}}, {"GSM1067242": {"DRINKING WATER": "distilled water containing 2mg/dl of sodium tungstate for 21 days", "GENOTYPE": "wild type"}}, {"GSM1067242": {"DRINKING WATER": "distilled water containing 2mg/dl of sodium tungstate for 21 days", "GENOTYPE": "wild type"}}, {"GSM1067244": {"DRINKING WATER": "distilled water for 21 days", "GENOTYPE": "Irs2 knockout (Irs2 -/-)"}}, {"GSM1067244": {"DRINKING WATER": "distilled water for 21 days", "GENOTYPE": "Irs2 knockout (Irs2 -/-)"}}, {"GSM1067246": {"DRINKING WATER": "distilled water containing 2mg/dl of sodium tungstate for 21 days", "GENOTYPE": "Irs2 knockout (Irs2 -/-)"}}, {"GSM1067246": {"DRINKING WATER": "distilled water containing 2mg/dl of sodium tungstate for 21 days", "GENOTYPE": "Irs2 knockout (Irs2 -/-)"}}], "id": 7136, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "Relative beta cell deficit and increased beta cell apoptosis are hallmarks of type 2 diabetes (T2D). The Insulin/Insulin Growth Factor...", "geo_gse_id": "E-GEOD-43620", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 2, "sample_count": 8, "tags": ["basal", "beta cell", "body", "cell", "central", "genome", "glucose", "insulin"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "effects-of-sodium-tungstate-administration-in-irs2", "geo_id_plat": "E-GEOD-43620_A-AFFY-45", "name": "Effects of sodium tungstate administration in Irs2 -/- mice", "created": "Nov.12, 2014", "summary": "Relative 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.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43620", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43620/samples/"}