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ACE2 over‐expression ameliorates glycemic homeostasis in diabetic mice
Author(s) -
Bindom Sharell M,
Feng Yumei,
Raju Sammeta VM,
Xia Huijing,
Lazartigues Eric
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1236.2
Subject(s) - glycemic , medicine , endocrinology , diabetes mellitus , pancreas , insulin
ACE inhibitor therapy has been shown to prevent new onset diabetes and pancreatic â‐cell dysfunction. We hypothesized that ACE2 would ameliorate glycemia in diabetic mice. Diabetic obese mice (db/db) and control lean littermates (db/m) were infected with a hACE2 or control (GFP) adenovirus (2x10e6 pfu 100 ìL) to the pancreas. After 7d, fasting blood glucose (12 hrs) and glucose tolerance (GT, 2 g/kg IP) were measured as indices of glycemic control. ACE2 immunofluorescence (arbitrary units) revealed high expression of hACE2 in the liver of mice infected with Ad‐hACE2 vs. Ad‐GFP (120±6 vs. 14±1, n=9, P<0.01), while hACE2 in the pancreas was not different between groups. Body weight (g) in db/db mice was not affected by Ad‐ACE2 (35±1, n=5) or Ad‐GFP (36±1 n=5) delivery. Baseline glycemia (mg/dL) was significantly higher in db/db vs. db/m mice (246±18 vs. 102±6, n=10, P<0.01) and was dramatically reduced in Ad‐hACE2‐ vs. Ad‐GFP‐treated db/db mice (157±12 vs. 203±6, n=5, P<0.05). Ad‐hACE2 infection had no effect on glycemia in db/m (92±8, n=10) compared to Ad‐GFP‐infected mice (75±10). In addition, Ad‐hACE2 infection significantly improved GT in db/db compared to GFP‐treated‐mice (573±43 vs. 749±18 mg/dL respectively, P<0.01) 1 hr post glucose administration. These data confirm the role of ACE2 in diabetes and suggest that ACE2 gene therapy can ameliorate glucose homeostasis in diabetic mice. (NIH NS052479 and RR018766)