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

Ellingsgaard, Helga
Hauselmann, Irina
Schuler, Beat
Habib, Abdella M
Baggio, Laurie L
Meier, Daniel T
Eppler, Elisabeth
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Published in Nature Medicine. 2011, vol. 17, no. 11, p. 1481-9
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 AnimalsBlood Glucose/metabolismCells, CulturedDiabetes Mellitus, Type 2/metabolism/physiopathologyDiet, High-FatDisease Models, AnimalEnteroendocrine Cells/drug effects/secretionFemaleGlucagon-Like Peptide 1/secretionGlucagon-Secreting Cells/drug effects/secretionGlucose Tolerance TestHumansInsulin/secretionInterleukin-6/antagonists & inhibitors/genetics/metabolism/pharmacologyMaleMiceMice, Inbred C57BLMice, TransgenicPhysical Conditioning, AnimalSignal Transduction/drug effects/physiology
PMID: 22037645
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Research group Fonction de l'îlot de Langerhans (324)
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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. 1481-9. doi: 10.1038/nm.2513 https://archive-ouverte.unige.ch/unige:25369

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Deposited on : 2013-01-10

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