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Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and α-cells

Ellingsgaard, H. and Hauselmann, I. and Schuler, B. and Habib, A. M. and Baggio, L. L. and Meier, D. T. and Eppler, E. and Bouzakri, K. and Wueest, S. and Muller, Y. D. and Hansen, A. M. and Reinecke, M. and Konrad, D. and Gassmann, M. and Reimann, F. and Halban, P. A. and Gromada, J. and Drucker, D. J. and Gribble, F. M. and Ehses, J. A. and Donath, M. Y.. (2011) Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and α-cells. Nature medicine, Vol. 17, H. 11. pp. 1481-1489.

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Official URL: http://edoc.unibas.ch/dok/A6004912

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Abstract

Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Infection Biology (Khanna)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Diabetes Research (Donath)
UniBasel Contributors:Donath, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing
ISSN:1078-8956
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:25 Oct 2013 08:32

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