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- Title
Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice.
- Authors
Bindom SM; Hans CP; Xia H; Boulares AH; Lazartigues E; Bindom, Sharell M; Hans, Chetan P; Xia, Huijing; Boulares, A Hamid; Lazartigues, Eric
- Abstract
<bold>Objective: </bold>Several clinical studies have shown the benefits of renin-angiotensin system (RAS) blockade in the development of diabetes, and a local RAS has been identified in pancreatic islets. Angiotensin I-converting enzyme (ACE)2, a new component of the RAS, has been identified in the pancreas, but its role in β-cell function remains unknown. Using 8- and 16-week-old obese db/db mice, we examined the ability of ACE2 to alter pancreatic β-cell function and thereby modulate hyperglycemia.<bold>Research Design and Methods: </bold>Both db/db and nondiabetic lean control (db/m) mice were infected with an adenovirus expressing human ACE2 (Ad-hACE2-eGFP) or the control virus (Ad-eGFP) via injection into the pancreas. Glycemia and β-cell function were assessed 1 week later at the peak of viral expression.<bold>Results: </bold>In 8-week-old db/db mice, Ad-hACE2-eGFP significantly improved fasting glycemia, enhanced intraperitoneal glucose tolerance, increased islet insulin content and β-cell proliferation, and reduced β-cell apoptosis compared with Ad-eGFP. ACE2 overexpression had no effect on insulin sensitivity in comparison with Ad-eGFP treatment in diabetic mice. Angiotensin-(1-7) receptor blockade by D-Ala(7)-Ang-(1-7) prevented the ACE2-mediated improvements in intraperitoneal glucose tolerance, glycemia, and islet function and also impaired insulin sensitivity in both Ad-hACE2-eGFP- and Ad-eGFP-treated db/db mice. D-Ala(7)-Ang-(1-7) had no effect on db/m mice. In 16-week-old diabetic mice, Ad-hACE2-eGFP treatment improved fasting blood glucose but had no effect on any of the other parameters.<bold>Conclusions: </bold>These findings identify ACE2 as a novel target for the prevention of β-cell dysfunction and apoptosis occurring in type 2 diabetes.
- Publication
Diabetes, 2010, Vol 59, Issue 10, p2540
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db09-0782