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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-7323

Ellingsgaard, H; Ehses, J A; Hammar, E B; Van Lommel, L; Quintens, R; Martens, G; Kerr-Conte, J; Pattou, F; Berney, T; Pipeleers, D; Halban, P A; Schuit, F C; Donath, M Y (2008). Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 105(35):13163-13168.

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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 alpha-cells relative to beta-cells, and alpha-cell dysfunction. Here we show that the alpha 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 alpha-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 alpha-cell proliferation, prevents apoptosis due to metabolic stress, and regulates alpha-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 alpha-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 alpha-cell mass display decreased fasting glucagon levels. However, despite these alpha-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 alpha-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.


99 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2 September 2008
Deposited On:10 Dec 2008 16:37
Last Modified:05 Apr 2016 12:40
Publisher:National Academy of Sciences
Additional Information:Copyright: National Academy of Sciences USA
Publisher DOI:10.1073/pnas.0801059105
PubMed ID:18719127

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