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Angiotensin II type...
Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes
- Article/chapterEnglish2006
Publisher, publication year, extent ...
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American Diabetes Association,2006
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-24724
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-24724URI
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https://doi.org/10.2337/diabetes.55.02.06.db05-1022DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
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Angiotensin II Type 1 Receptor Blockers/*pharmacology/*therapeutic use
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Animals
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Blood Glucose/drug effects
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Diabetes Mellitus; Type 2/*drug therapy/genetics
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Disease Models; Animal
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Gene Expression Regulation
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Glucose Intolerance/*drug therapy
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Insulin/metabolism
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Insulin-Secreting Cells/cytology/*drug effects/metabolism/physiology
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Losartan/*pharmacology/therapeutic use
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Mice
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Mice; Obese
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Proinsulin/biosynthesis
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Receptor; Angiotensin; Type 1/genetics/*metabolism
Added entries (persons, corporate bodies, meetings, titles ...)
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Lau, Tung
(author)
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Carlsson, Per-OlaUppsala universitet,Institutionen för medicinsk cellbiologi,Endokrin diabetes och metabolism(Swepub:uu)perocarl
(author)
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Leung, Po Sing
(author)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Related titles
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In:Diabetes: American Diabetes Association55:2, s. 367-3740012-17971939-327X
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