Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

LRRC8/VRAC anion channels enhance β-cell glucose sensing and insulin secretion

[img]
Preview
PDF (Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB
[img]
Preview
PDF (Supplementary Information) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:LRRC8/VRAC anion channels enhance β-cell glucose sensing and insulin secretion
Creators Name:Stuhlmann, T. and Planells-Cases, R. and Jentsch, T.J.
Abstract:Glucose homeostasis depends critically on insulin that is secreted by pancreatic β-cells. Serum glucose, which is directly sensed by β-cells, stimulates depolarization- and Ca(2+)-dependent exocytosis of insulin granules. Here we show that pancreatic islets prominently express LRRC8A and LRRC8D, subunits of volume-regulated VRAC anion channels. Hypotonicity- or glucose-induced β-cell swelling elicits canonical LRRC8A-dependent VRAC currents that depolarize β-cells to an extent that causes electrical excitation. Glucose-induced excitation and Ca(2+) responses are delayed in onset, but not abolished, in β-cells lacking the essential VRAC subunit LRRC8A. Whereas Lrrc8a disruption does not affect tolbutamide- or high-K(+)-induced insulin secretion from pancreatic islets, it reduces first-phase glucose-induced insulin secretion. Mice lacking VRAC in β-cells have normal resting serum glucose levels but impaired glucose tolerance. We propose that opening of LRRC8/VRAC channels increases glucose sensitivity and insulin secretion of β-cells synergistically with K(ATP) closure. Neurotransmitter-permeable LRRC8D-containing VRACs might have additional roles in autocrine/paracrine signaling within islets.
Keywords:Animal Models, Blood Glucose, Glucose, Hypoglycemic Agents, Inbred C57BL Mice, Insulin, Insulin-Secreting Cells, Inwardly Rectifying Potassium Channels, Ion Channels, Membrane Proteins, Primary Cell Culture, Protein Multimerization, Tolbutamide, Transgenic Mice, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:9
Number:1
Page Range:1974
Date:17 May 2018
Official Publication:https://doi.org/10.1038/s41467-018-04353-y
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library