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Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. 2011
Helga Ellingsgaard, and
Irina Hauselmann, and
Beat Schuler, and
Abdella M Habib, and
Laurie L Baggio, and
Daniel T Meier, and
Elisabeth Eppler, and
Karim Bouzakri, and
Stephan Wueest, and
Yannick D Muller, and
Ann Maria Kruse Hansen, and
Manfred Reinecke, and
Daniel Konrad, and
Max Gassmann, and
Frank Reimann, and
Philippe A Halban, and
Jesper Gromada, and
Daniel J Drucker, and
Fiona M Gribble, and
Jan A Ehses, and
Marc Y Donath
Clinic for Endocrinology, Diabetes & Metabolism and Department Biomedicine, University Hospital Basel, Basel, Switzerland. helga.ellingsgaard@unibas.ch
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.
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