Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion.

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion.
Diabetes. 2014 Oct 2;
Authors: Hashimoto S, Kubota N, Sato H, Sasaki M, Takamoto I, Kubota T, Nakaya K, Noda M, Ueki K, Kadowaki T
Abstract
Endothelial cells are considered to be essential for normal pancreatic β-cell function. The present study attempted to demonstrate the role of Irs2 in endothelial cells with regard to insulin secretion. Endothelial cell-specific insulin receptor substrate-2 knockout (ETIrs2KO) mice exhibited impaired glucose-induced, arginine-induced, and glucagon-induced insulin secretion and showed glucose intolerance. In batch incubation and perifusion experiments using isolated islets, glucose-induced insulin secretion was not significantly different between the control and the ETIrs2KO mice. In contrast, in perfusion experiments, glucose-induced insulin secretion was significantly impaired in the ETIrs2KO mice. The islet blood flow was significantly impaired in the ETIrs2KO mice. Following the treatment of these knockout mice with enalapril maleate, which improved the islet blood flow, glucose-stimulated insulin secretion was almost completely restored to levels equal to those in the control mice. These data suggest that Irs2 deletion in endothelial cells leads to a decreased islet blood flow, which may cause impaired glucose-induced insulin secretion. Thus, Irs2 in endothelial cells may serve as a novel ther...

Source: Diabetes - October 2, 2014 Category: Endocrinology Authors: Hashimoto S, Kubota N, Sato H, Sasaki M, Takamoto I, Kubota T, Nakaya K, Noda M, Ueki K, Kadowaki T Tags: Diabetes Source Type: research