Dataset Information

Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice.

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 ?-cell function remains unknown. Using 8- and 16-week-old obese db/db mice, we examined the ability of ACE2 to alter pancreatic ?-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 ?-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 ?-cell proliferation, and reduced ?-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.

Conclusions

These findings identify ACE2 as a novel target for the prevention of ?-cell dysfunction and apoptosis occurring in type 2 diabetes.

SUBMITTER: Bindom SM

PROVIDER: S-EPMC3279528 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice.

Bindom Sharell M SM Hans Chetan P CP Xia Huijing H Boulares A Hamid AH Lazartigues Eric E

Diabetes 20100726 10

<h4>Objective</h4>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. ...[more]

PMID: 20660625

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Dataset Information

Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice.

Objective

Research design and methods

Results

Conclusions

Publications

Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice.

Similar Datasets

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