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Shortcomings of current models of glucose‐induced insulin secretion
Author(s) -
Henquin J. C.,
Nenquin M.,
Ravier M. A.,
Szollosi A.
Publication year - 2009
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2009.01109.x
Subject(s) - depolarization , exocytosis , insulin , secretion , medicine , biophysics , endocrinology , carbohydrate metabolism , cytosol , membrane potential , biology , beta cell , chemistry , microbiology and biotechnology , biochemistry , enzyme , islet
Glucose‐induced insulin secretion by pancreatic β‐cells is generally schematized by a ‘consensus model’ that involves the following sequence of events: acceleration of glucose metabolism, closure of ATP‐sensitive potassium channels (K ATP channels) in the plasma membrane, depolarization, influx of Ca 2+ through voltage‐dependent calcium channels and a rise in cytosolic‐free Ca 2+ concentration that induces exocytosis of insulin‐containing granules. This model adequately depicts the essential triggering pathway but is incomplete. In this article, we first make a case for a model of dual regulation in which a metabolic amplifying pathway is also activated by glucose and augments the secretory response to the triggering Ca 2+ signal under physiological conditions. We next discuss experimental evidence, largely but not exclusively obtained from β‐cells lacking K ATP channels, which indicates that these channels are not the only possible transducers of glucose effects on the triggering Ca 2+ signal. We finally address the identity of the widely neglected background inward current (Cl − efflux vs. Na + or Ca 2+ influx through voltage‐independent channels) that is necessary to cause β‐cell depolarization when glucose closes K ATP channels. More attention should be paid to the possibility that some components of this background current are influenced by glucose metabolism and have their place in a model of glucose‐induced insulin secretion.