Premium
Aldose reductase deficiency enhances high fat diet‐induced hyper‐insulinemia and endothelial dysfunction
Author(s) -
Mehta Ishan,
Conklin Daniel,
Srivastava Sanjay,
Bhatnagar Aruni
Publication year - 2010
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.24.1_supplement.981.8
Subject(s) - medicine , endocrinology , endothelial dysfunction , hyperinsulinemia , aldose reductase , diabetes mellitus , type 2 diabetes , obesity , oxidative stress , endothelium , lipid peroxidation , cholesterol , insulin , glucose tolerance test , insulin resistance , chemistry
Obesity and Type II diabetes enhance cardiovascular disease risk 2–9 times and are reaching epidemic levels in the U.S. with ~16 million diabetics and >30 million obese people. Because endothelial dysfunction is associated with high fat intake and increased cardiovascular disease risk, we studied the relationship between high fat diet (HFD), endothelial dysfunction and aldose reductase (AR), a glucose‐ and aldehyde‐metabolizing enzyme. Thus, we fed young male C57BL/6 and AR‐null mice a normal chow (NC; 21% kcal fat) or HFD (42% kcal fat) for 12 weeks. HFD significantly increased glucose intolerance, plasma cholesterol, and plasma insulin in both C57BL/6 and AR‐null mice compared with NC‐fed mice, but HFD induced a greater hyperinsulinemia in AR‐null compared with HFD‐fed C57BL/6 mice. Similarly, HFD significantly decreased aortic endothelial‐dependent relaxation only in AR‐null mice. Also HFD depressed plasma NOx to a greater degree in AR‐null mice. Collectively, these data indicate that AR deficiency specifically enhances HFD‐induced endothelial dysfunction by decreasing NO production and/or bioavailability. We conclude that AR deficiency enhances the sensitivity of the endothelium to oxidative stress induced by HFD perhaps via loss of AR‐mediated detoxification of lipid peroxidation‐derived aldehydes. This study supported by UofL Diabetes and Obesity Center P20RR024489 and NIEHS T35 ES014559.