ACE2 GENE THERAPY PREVENTS ANGIOTENSIN II-MEDIATED IMPAIRED GLUCOSE TOLERANCE AND INSULIN RESISTANCE IN MICE.
Document Type
Presentation
Start Date
22-10-2010 1:15 PM
End Date
22-10-2010 1:30 PM
Description
The renin-angiotensin system (RAS) plays a key role in the progression of type 2 diabetes. ACE2 is a recently discovered enzyme that counteracts RAS over activity by cleaving angiotensin (Ang) II into Ang (1-7). We hypothesized that Ang II can mediate impaired glucose tolerance (IGT) and insulin resistance (IR) and ACE2 can prevent Ang II-mediated effects. To determine if Ang II can mediate !GT and IR, we infused C57BL/6 mice (N=5) with Ang II (osmotic pumps; 600 ng/Kg.min1) or saline for 14 days. After 14 days of Ang II infusion, we determined glucose tolerance (AUC: mg/di x 120) and measured plasma insulin levels (ng/ml). Ang II-infused mice exhibited significantly (p<0.05) higher !GT (32736 ± 1731 vs. 24065 ± 1940) and plasma insulin levels (4.76 ± 0.19 vs. 2.91 ± 0.15) compared to saline-infused mice, suggesting Ang II can mediate !GT and IR. To test the therapeutic· potential of ACE2, we treated Ang II infused mice with ACE2 gene/GFP gene (injected into the pancreas of mice) at the ih day of 14 days infusion. ACE2 treated Ang II-infused mice had significantly lower IGT (25067 ± 845 vs. 30259 ± 1279) and insulin levels (3.49 ± 0.1375 vs. 4.55 ± 0.23) compared to control suggesting beneficial effects of ACE2. Altogether, Ang II can mediate IGT and IR and ACE2 can prevent Ang II-mediated detrimental effects in mice. In conclusion, we suggest that ACE2 can be a potential therapeutic agent for Ang II-mediated IGT and IR.
Support-American Diabetes Association (1_10_BS_93) -National Institutes of Health (DK084466)
Recommended Citation
Chhabra, Kavaljit and Lazartigues, E., "ACE2 GENE THERAPY PREVENTS ANGIOTENSIN II-MEDIATED IMPAIRED GLUCOSE TOLERANCE AND INSULIN RESISTANCE IN MICE." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 2.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation2/2
ACE2 GENE THERAPY PREVENTS ANGIOTENSIN II-MEDIATED IMPAIRED GLUCOSE TOLERANCE AND INSULIN RESISTANCE IN MICE.
The renin-angiotensin system (RAS) plays a key role in the progression of type 2 diabetes. ACE2 is a recently discovered enzyme that counteracts RAS over activity by cleaving angiotensin (Ang) II into Ang (1-7). We hypothesized that Ang II can mediate impaired glucose tolerance (IGT) and insulin resistance (IR) and ACE2 can prevent Ang II-mediated effects. To determine if Ang II can mediate !GT and IR, we infused C57BL/6 mice (N=5) with Ang II (osmotic pumps; 600 ng/Kg.min1) or saline for 14 days. After 14 days of Ang II infusion, we determined glucose tolerance (AUC: mg/di x 120) and measured plasma insulin levels (ng/ml). Ang II-infused mice exhibited significantly (p<0.05) higher !GT (32736 ± 1731 vs. 24065 ± 1940) and plasma insulin levels (4.76 ± 0.19 vs. 2.91 ± 0.15) compared to saline-infused mice, suggesting Ang II can mediate !GT and IR. To test the therapeutic· potential of ACE2, we treated Ang II infused mice with ACE2 gene/GFP gene (injected into the pancreas of mice) at the ih day of 14 days infusion. ACE2 treated Ang II-infused mice had significantly lower IGT (25067 ± 845 vs. 30259 ± 1279) and insulin levels (3.49 ± 0.1375 vs. 4.55 ± 0.23) compared to control suggesting beneficial effects of ACE2. Altogether, Ang II can mediate IGT and IR and ACE2 can prevent Ang II-mediated detrimental effects in mice. In conclusion, we suggest that ACE2 can be a potential therapeutic agent for Ang II-mediated IGT and IR.
Support-American Diabetes Association (1_10_BS_93) -National Institutes of Health (DK084466)
Comments
See abstract book page 38