title: First phase insulin secretion and 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.
authors: Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia.
authors: K
authors: K
authors: Cheng
authors: S
authors: S
authors: Andrikopoulos
authors: J E
authors: JE
authors: Gunton
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D055106:Genome-Wide Association Study; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D009250:NADP Transhydrogenases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D009250:NADP Transhydrogenases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D005941:Glucokinase; D011972:Receptor, Insulin; C497446:VHL protein, human; D005947:Glucose