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- Title
Angiotensin I--Converting Enzyme Type 2 (ACE2) Gene Therapy Improves Glycemic Control in Diabetic Mice.
- Authors
Bindom, Sharell M.; Hans, Chetan P.; Huijing Xia; Boulares, A. Hamid; Lazartigues, Eric
- Abstract
OBJECTIVE--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. RESEARCH DESIGN AND METHODS--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. RESULTS--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-Ala7-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-Ala7--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. CONCLUSIONS--These findings identify ACE2 as a novel target for the prevention of β-cell dysfunction and apoptosis occurring in type 2 diabetes. Diabetes 59:2540-2548, 2010
- Subjects
DIABETES; RENIN-angiotensin system; GENE therapy; ANGIOTENSIN converting enzyme; PANCREATIC beta cells; HYPERGLYCEMIA
- Publication
Diabetes, 2010, Vol 59, Issue 10, p2540
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db09-0782