Distinct Role for ARNT/HIF-1β in Pancreatic Beta-Cell Function, Insulin Secretion and Type 2 Diabetes

Abstract

Diabetes mellitus is a common metabolic syndrome that has become an epidemic in modern society and is characterized by either a near-complete lack of insulin production due to autoimmune destruction of pancreatic beta-cells as in type 1 diabetes or abnormal insulin secretion, beta-cell dysfunction and insulin resistance as in type 2 diabetes (T2D). T2D is a complex heterogeneous disease that is characterized by elevated fasting and postprandial blood glucose levels that can result in severe complications including renal failure, cardiovascular disease, blindness and slow wound healing (Lin and Sun, 2010). Pancreatic islet beta-cells play a critical role in maintaining blood glucose levels by secreting the hormone insulin following a meal. Insulin maintains blood glucose levels in the normal physiological range by promoting glucose uptake in muscles, liver and adipose tissue, and by inhibiting hepatic glucose production. Therefore, any defect in insulin secretion in response to a meal or defects in insulin action in peripheral tissues can lead to increased blood glucose levels (Tripathy and Chavez, 2010; Muoio & Newgard, 2008).