title: Glucose-induced inhibition of insulin secretion.
abstract: Increase in glucose is known to elevate the concentration of cytoplasmic Ca(2+) ([Ca(2+) ]i ) in pancreatic β-cells and stimulate insulin secretion. However, rise of glucose can also lower [Ca(2+) ]i and inhibit insulin release. In the present review, we examine the mechanisms for this inhibition and highlight its importance for the healthy β-cell and the development of diabetes. It is possible to distinguish between 60 and 90 s of prompt inhibition and the late inhibition seen after the first-phase peak of insulin release. The introductory inhibition is characteristic of the healthy β-cell and mediated by sequestration of [Ca(2+) ]i in the endoplasmic reticulum. This inhibition is easily seen in studies of isolated islets but too brief to be detected in a conventional intravenous glucose tolerance test. Coupled to simultaneous rise of glucagon, the introductory suppression of insulin release is the starting point for the antiphase relation between the subsequent insulin and glucagon pulses. Another effect of the initial suppression is to increase the pool of readily releasable granules responsible for the first-phase release of insulin. The presence of late inhibition of insulin release is an indicator of β-cell dysfunction. Patients with type 2 diabetes often respond to intravenous bolus injection of glucose with 5-10 min of late suppression of circulating insulin.
authors.affiliation: Department of Medical Cell Biology, University of Uppsala, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Hellman
authors.forename: E
authors.initials: E
authors.lastname: Grapengiesser
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose; D002118:Calcium
keywords: cytoplasmic Ca2+; diabetes; glucose; insulin; pulsatile release; β-cell