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Angiotensin II Induces Interleukin-1β–Mediated Islet Inflammation and β-Cell Dysfunction Independently of Vasoconstrictive Effects

Sauter, N. S. and Thienel, C. and Plutino, Y. and Kampe, K. and Dror, E. and Traub, S. and Timper, K. and Bedat, B. and Pattou, F. and Kerr-Conte, J. and Jehle, A. W. and Boni-Schnetzler, M. and Donath, M. Y.. (2015) Angiotensin II Induces Interleukin-1β–Mediated Islet Inflammation and β-Cell Dysfunction Independently of Vasoconstrictive Effects. Diabetes, 64 (4). pp. 1273-1283.

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Official URL: https://edoc.unibas.ch/61696/

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Abstract

Pathological activation of the renin-angiotensin system (RAS) is associated with the metabolic syndrome, and the new onset of type 2 diabetes can be delayed by RAS inhibition. In animal models of type 2 diabetes, inhibition of the RAS improves insulin secretion. However, the direct effects of angiotensin II on islet function and underlying mechanisms independent of changes in blood pressure remain unclear. Here we show that exposure of human and mouse islets to angiotensin II induces interleukin (IL)-1-dependent expression of IL-6 and MCP-1, enhances beta-cell apoptosis, and impairs mitochondrial function and insulin secretion. In vivo, mice fed a high-fat diet and treated with angiotensin II and the vasodilator hydralazine to prevent hypertension showed defective glucose-stimulated insulin secretion and deteriorated glucose tolerance. Application of an anti-IL-1beta antibody reduced the deleterious effects of angiotensin II on islet inflammation, restored insulin secretion, and improved glycemia. We conclude that angiotensin II leads to islet dysfunction via induction of inflammation and independent of vasoconstriction. Our findings reveal a novel role for the RAS and an additional rationale for the treatment of type 2 diabetic patients with an IL-1beta antagonist.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Diabetes Research (Donath)
UniBasel Contributors:Donath, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Diabetes Association
ISSN:0012-1797
e-ISSN:1939-327X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:01 Nov 2018 18:27
Deposited On:16 Oct 2018 17:18

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