期刊
DIABETES
卷 62, 期 4, 页码 1084-1093出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-1139
关键词
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资金
- American Federation for Aging Research
- Mayo Foundation
- Strickland Career Development Award
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) [DK-084055]
- Mayo-UOFM Decade of Discovery Grant [63-01]
- Minnesota Obesity Council Grant [DK-50456-15]
- NIH/National Institute on Aging
- Juvenile Diabetes Research Foundation
- United Mitochondrial Disease Foundation
- Glenn Foundation for Medical Research
- American Heart Association postdoctoral fellowship award [11POST7320060]
- Portuguese Foundation for Science and Technology [SFRH/BD/44674/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/44674/2008] Funding Source: FCT
Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD(+) metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD(+) levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD(+)ase in mammals. Moreover, CD38 knockout mice have higher NAD(+) levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD(+) levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD(+) levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD(+) levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD(+)-dependent pathways. Diabetes 62:1084-1093, 2013
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