Journal
DIABETES RESEARCH AND CLINICAL PRACTICE
Volume 93, Issue -, Pages S27-S31Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0168-8227(11)70010-9
Keywords
Biphasic insulin secretion; Beta cell; Insulin release; Arginine; Sulfonylureas; Type 2 diabetes
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Funding
- Fonds de la Recherche Scientifique et Medicale, Brussels, Belgium
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This review outlines the two pathways that interact in beta-cells to ensure temporal and amplitude control of insulin secretion by glucose. The most well known triggering pathway involves the following steps: acceleration of glucose metabolism, closure of ATP-sensitive potassium channels, depolarization, influx of Ca(2+) through voltage-gated calcium channels, and a rise in the concentration of cytosolic ionized Ca(2+) that triggers exocytosis of insulin-containing granules. This classic sequence is, however, incomplete. Additional mechanisms, involving other channels, are necessarily implicated in the production of the triggering Ca(2+) signal. It is also clear that the effect of glucose on insulin secretion would be poor if Ca(2+)-induced exocytosis was not markedly augmented (approximately doubled) through a metabolic amplifying pathway, mechanistically distinct from neurohormonal amplifying pathways. This metabolic amplifying pathway is physiologically relevant for both phases of glucose-induced insulin secretion and for the potentiation, by glucose, of insulin secretion triggered by non-metabolized secretagogues (e.g. arginine). Three important challenges for future studies will be to identify the additional targets mediating control of the triggering Ca(2+) signal by glucose, to elucidate the cellular mechanisms of the metabolic amplifying pathway and to determine the contribution of each pathway in the alterations of insulin secretion in type 2 diabetic patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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