GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet {beta}-Cell Function and Survival

Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of β-cells and improved glucose metabolism in both nongenetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused β-cell failure and lethal T2D. In vitro treatment of isolated murine islets and MIN6 cells with recombinant GDF11 attenuated glucotoxicity-induced β-cell dysfunction and apoptosis. Mechanistically, the GDF11-mediated protective effects could be attributed to the activation of transforming growth factor-β/Smad2 and phosphatidylinositol-4,5-bisphosphate 3-kinase–AKT–FoxO1 signaling. These findings suggest that GDF11 repletion may improve β-cell function and mass and thus may lead to a new therapeutic approach for T2D.
Source: Diabetes - Category: Endocrinology Authors: Tags: Islet Biology-Apoptosis Islet Studies Source Type: research