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Diabetes. 2010 Apr;59(4):829-35. doi: 10.2337/db09-1191. Epub 2010 Jan 27.

SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity.

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1
Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.

Abstract

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 DeltaEE (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 hyperinsulinemic-euglycemic 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-1beta, 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] 1alpha 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.

PMID:
20107110
PMCID:
PMC2844830
DOI:
10.2337/db09-1191
[Indexed for MEDLINE]
Free PMC Article
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