期刊
DIABETES
卷 59, 期 4, 页码 829-835出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-1191
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资金
- Academy of Finland
- EU [EUGENE2, LSHM-CT-2004-512013]
- Centre National de la Recherche Scientifique
- Institut National de la Sante et de la Recherche Medicale
- Universite Louis Pasteur
- Ecole Polytechnique Federale de Lausanne
- National Institutes of Health [DK069966]
- Fondation Recherche Medicale
OBJECTIVE-Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESIGN AND METHODS-Energy expenditure (EE), insulin sensitivity, and SIRT1 mRNA adipose tissue expression (n = 81) were measured by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and quantitative RT-PCR in 247 nondiabetic offspring of type 2 diabetic patients. RESULTS-High EE during the clamp (r = 0.375, P = 2.8 x 10(-9)) and high Delta EE (EE during the clamp - EE in the fasting state) (r = 0.602, P = 2.5 x 10(-24)) were associated with high insulin sensitivity. Adipose tissue SIRT1 mRNA expression was significantly associated with EE (r = 0.289, P = 0.010) and with insulin sensitivity (r = 0.334, P = 0.002) during hyperinsulinemiceuglycemic clamp. Furthermore, SIRT1 mRNA expression correlated significantly with the expression of several genes regulating mitochondrial function and energy metabolism (e.g., peroxisome proliferator-activated receptor gamma coactivator-1 beta, estrogen-related receptor alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), and with several genes of the respiratory chain (e.g., including NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 2, cytochrome c, cytochrome c oxidase subunit IV, and ATP synthase). CONCLUSIONS-Impaired stimulation of EE by insulin and low SIRT1 expression in insulin-sensitive tissues is likely to reflect impaired regulation of mitochondrial function associated with insulin resistance in humans. Diabetes 59:829-835, 2010
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