Interleukin-6 Enhances Insulin Secretion by Increasing Glucagon-like Peptide-1 Secretion from L Cells and Alpha Cells

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2011 Nov 1

PMID 22037645

Citations 405

Authors

Helga Ellingsgaard

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

Soon will be listed here.

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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