Title: Interleukin-6 regulates pancreatic alpha-cell mass expansion
Authors: Ellingsgaard, Helga ×
Ehses, Jan A
Hammar, Eva B
Van Lommel, Leentje
Quintens, Roel
Martens, Geert
Kerr-Conte, Julie
Pattou, Francois
Berney, Thierry
Pipeleers, Daniel
Halban, Philippe A
Schuit, Frans
Donath, Marc Y #
Issue Date: Sep-2008
Publisher: Natl acad sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:105 issue:35 pages:13163-13168
Abstract: Interleukin-6 (IL-6) is systemically elevated in obesity and is a predictive factor to develop type 2 diabetes. Pancreatic islet pathology in type 2 diabetes is characterized by reduced beta-cell function and mass, an increased proportion of a-cells relative to p-cells, and a-cell dysfunction. Here we show that the a cell is a primary target of IL-6 actions. Beginning with investigating the tissue-specific expression pattern of the IL-6 receptor (IL-6R) in both mice and rats, we find the highest expression of the IL-6R in the endocrine pancreas, with highest expression on the a-cell. The islet IL-6R is functional, and IL-6 acutely regulates both pro-glucagon mRNA and glucagon secretion in mouse and human islets, with no acute effect on insulin secretion. Furthermore, IL-6 stimulates a-cell proliferation, prevents apoptosis due to metabolic stress, and regulates a-cell mass in vivo. Using IL-6 KO mice fed a high-fat diet, we find that IL-6 is necessary for high-fat diet-induced increased a-cell mass, an effect that occurs early in response to diet change. Further, after high-fat diet feeding, IL-6 KO mice without expansion of a-cell mass display decreased fasting glucagon levels. However, despite these a-cell effects, high-fat feeding of IL-6 KO mice results in increased fed glycemia due to impaired insulin secretion, with unchanged insulin sensitivity and similar body weights. Thus, we conclude that IL-6 is necessary for the expansion of pancreatic a-cell mass in response to high-fat diet feeding, and we suggest that this expansion may be needed for functional beta-cell compensation to increased metabolic demand.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
× corresponding author
# (joint) last author

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