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
  • 1. Clinic for Endocrinology, Diabetes & Metabolism and Department Biomedicine, University Hospital Basel, Basel, Switzerland. [email protected]
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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