PT  - JOURNAL ARTICLE
AU  - Chu, Kwan Yi
AU  - Lau, Tung
AU  - Carlsson, Per-Ola
AU  - Leung, Po Sing
TI  - Angiotensin II Type 1 Receptor Blockade Improves β-Cell Function and Glucose Tolerance in a Mouse Model of Type 2 Diabetes
AID  - 10.2337/diabetes.55.02.06.db05-1022
DP  - 2006 Feb 01
TA  - Diabetes
PG  - 367--374
VI  - 55
IP  - 2
4099  - http://diabetes.diabetesjournals.org/content/55/2/367.short
4100  - http://diabetes.diabetesjournals.org/content/55/2/367.full
SO  - Diabetes2006 Feb 01; 55
AB  - 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 β-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 β-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.