2. Academic Validation
  3. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells

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

  • Nat Med. 2011 Oct 30;17(11):1481-9. doi: 10.1038/nm.2513.
Helga Ellingsgaard 1,  Irina Hauselmann,  Beat Schuler,  Abdella M Habib,  Laurie L Baggio,  Daniel T Meier,  Elisabeth Eppler,  Karim Bouzakri,  Stephan Wueest,  Yannick D Muller,  Ann Maria Kruse Hansen,  Manfred Reinecke,  Daniel Konrad,  Max Gassmann,  Frank Reimann,  Philippe A Halban,  Jesper Gromada,  Daniel J Drucker,  Fiona M Gribble,  Jan A Ehses,  Marc Y Donath
Affiliations

Affiliation

  • 1 Clinic for Endocrinology, Diabetes & Metabolism and Department Biomedicine, University Hospital Basel, Basel, Switzerland. helga.ellingsgaard@unibas.ch
PMID: 22037645 DOI: 10.1038/nm.2513
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.

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