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Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
2006 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 2, 367-374 p.Article in journal (Refereed) Published
Abstract [en]

We identified an angiotensin-generating system in pancreatic islets and found that exogenously administered angiotensin II, after binding to its receptors (angiotensin II type 1 receptor [AT1R]), inhibits insulin release in a manner associated with decreased islet blood flow and (pro)insulin biosynthesis. The present study tested the hypothesis that there is a change in AT1R expression in the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db mouse, which enables endogenous levels of angiotensin II to impair islet function. Islets from 10-week-old db/db and control mice were isolated and investigated. In addition, the AT1R antagonist losartan was administered orally to 4-week-old db/db mice for an 8-week period. We found that AT1R mRNA was upregulated markedly in db/db islets and double immunolabeling confirmed that the AT1R was localized to beta-cells. Losartan selectively improved glucose-induced insulin release and (pro)insulin biosynthesis in db/db islets. Oral losartan treatment delayed the onset of diabetes, and reduced hyperglycemia and glucose intolerance in db/db mice, but did not affect the insulin sensitivity of peripheral tissues. The present findings indicate that AT1R antagonism improves beta-cell function and glucose tolerance in young type 2 diabetic mice. Whether islet AT1R activation plays a role in the pathogenesis of human type 2 diabetes remains to be determined.

Place, publisher, year, edition, pages
2006. Vol. 55, no 2, 367-374 p.
Keyword [en]
Angiotensin II Type 1 Receptor Blockers/*pharmacology/*therapeutic use, Animals, Blood Glucose/drug effects, Diabetes Mellitus; Type 2/*drug therapy/genetics, Disease Models; Animal, Gene Expression Regulation, Glucose Intolerance/*drug therapy, Insulin/metabolism, Insulin-Secreting Cells/cytology/*drug effects/metabolism/physiology, Losartan/*pharmacology/therapeutic use, Mice, Mice; Obese, Proinsulin/biosynthesis, Receptor; Angiotensin; Type 1/genetics/*metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-24724DOI: 10.2337/diabetes.55.02.06.db05-1022PubMedID: 16443769OAI: oai:DiVA.org:uu-24724DiVA: diva2:52498
Available from: 2007-02-07 Created: 2007-02-07 Last updated: 2013-04-03Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16443769&dopt=Citation

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Carlsson, Per-Ola
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