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Scientific article
Open access
English

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

Published inNature medicine, vol. 17, no. 11, p. 1481-1489
Publication date2011
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.

Keywords
  • Animals
  • Blood Glucose/metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Type 2/metabolism/physiopathology
  • Diet, High-Fat
  • Disease Models, Animal
  • Enteroendocrine Cells/drug effects/secretion
  • Female
  • Glucagon-Like Peptide 1/secretion
  • Glucagon-Secreting Cells/drug effects/secretion
  • Glucose Tolerance Test
  • Humans
  • Insulin/secretion
  • Interleukin-6/antagonists & inhibitors/genetics/metabolism/pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Physical Conditioning, Animal
  • Signal Transduction/drug effects/physiology
Citation (ISO format)
ELLINGSGAARD, Helga et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. In: Nature medicine, 2011, vol. 17, n° 11, p. 1481–1489. doi: 10.1038/nm.2513
Main files (1)
Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal1078-8956
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685downloads

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