Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells.
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.
Clinic for Endocrinology, Diabetes & Metabolism and Department Biomedicine, University Hospital Basel, Basel, Switzerland. helga.ellingsgaard@unibas.ch
Helga
H
Ellingsgaard
Irina
I
Hauselmann
Beat
B
Schuler
Abdella M
AM
Habib
Laurie L
LL
Baggio
Daniel T
DT
Meier
Elisabeth
E
Eppler
Karim
K
Bouzakri
Stephan
S
Wueest
Yannick D
YD
Muller
Ann Maria Kruse
AM
Hansen
Manfred
M
Reinecke
Daniel
D
Konrad
Max
M
Gassmann
Frank
F
Reimann
Philippe A
PA
Halban
Jesper
J
Gromada
Daniel J
DJ
Drucker
Fiona M
FM
Gribble
Jan A
JA
Ehses
Marc Y
MY
Donath
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D007328:Insulin; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors