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Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S27-31. doi: 10.1016/S0168-8227(11)70010-9.

The dual control of insulin secretion by glucose involves triggering and amplifying pathways in β-cells.

Author information

1
Unit of Endocrinology and Metabolism, University of Louuain Faculty of Medicine, Brussels, Belgium. jean-claude.henquin@uclouvain.be

Abstract

This review outlines the two pathways that interact in β-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.

PMID:
21864748
DOI:
10.1016/S0168-8227(11)70010-9
[Indexed for MEDLINE]

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