Title:First Phase Insulin Secretion and Type 2 Diabetes
Volume: 13
Issue: 1
Author(s): K. Cheng, S. Andrikopoulos and J. E. Gunton
Affiliation:
Keywords:
Aryl hydrocarbon nuclear translocator, glucose homeostasis, hypoxia inducible factor-1α, insulin
secretion, regulatory genes, type 2 diabetes
Abstract: Type 2 diabetes (T2D) is a metabolic disorder characterised by the inability of β-cells to secrete
enough insulin to maintain glucose homeostasis. Pancreatic β-cells secrete insulin in a biphasic manner, first
and second phase insulin secretion, and loss of first phase insulin secretion is an independent predictor of T2D
onset. Restoration of first phase insulin secretion has been shown to improve blood glucose in T2D by
suppressing hepatic glucose production and priming insulin sensitive tissue to more readily take up glucose
and has thus prompted numerous studies into its regulation. First phase insulin secretion is initiated primarily
by the classical triggering pathway, a complex system comprised of multiple stimulatory signals. Recent
studies have identified a number of novel regulatory factors that are crucial for first phase insulin secretion and
glucose homeostasis. These include, among others, hypoxia inducible factor 1α, von Hippel-Lindau, factor
inhibiting HIF, nicotinamide phospho-ribosyl-transferase, and the sirtuin family. This review will outline how first
phase insulin secretion is initiated and detail some of the recent findings in its regulation.
