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- Title
Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells.
- Authors
Ellingsgaard, Helga; Hauselmann, Irina; Schuler, Beat; Habib, Abdella M; Baggio, Laurie L; Meier, Daniel T; Eppler, Elisabeth; Bouzakri, Karim; Wueest, Stephan; Muller, Yannick D; Hansen, Ann Maria Kruse; Reinecke, Manfred; Konrad, Daniel; Gassmann, Max; Reimann, Frank; Halban, Philippe A; Gromada, Jesper; Drucker, Daniel J; Gribble, Fiona M; Ehses, Jan A; Donath, Marc Y
- 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.
- Publication
Nature medicine, 2011, Vol 17, Issue 11, p1481
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.2513