Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes |
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| Institution: | 1. Department of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju, South Korea;2. Diabetes Research Institute, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea;3. Department of Endocrinology and Metabolism, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea;1. Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany;2. LIFE Leipzig Research Centre for Civilization Diseases, University of Leipzig, Philipp-Rosenthalstr. 27, D-04103 Leipzig, Germany;3. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;4. Department of Biology, Laboratory for Genomics and Molecular Biomedicine, Faculty of Science, University of Copenhagen, Copenhagen, Denmark;5. Institut für Medizinische Physik und Biophysik, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany;1. Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA;2. Department of Cardiology, Tongji Hospital, Tongji University, Shanghai 20065, China;3. Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA;4. Electron Microscopy Core Facility, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA;5. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;1. Department of Nutrition, China Medical University, Taichung, Taiwan;2. Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan;3. Hualien District Agricultural Research and Extension Station, Hualien, Taiwan;1. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612;2. College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, PR China;3. Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, 150086, PR China;4. Department of Pathology, University of Illinois, Medical Center, Chicago, IL 60612;1. Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China;2. Department of Pharmacology, Second Military Medical University, Shanghai, China;1. Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, USA;2. Pharmacology and Physiology, University of Rochester Medical Center, USA;3. Department of Medicine, University of Rochester Medical Center, USA;4. Department of Biochemistry, University of Rochester Medical Center, USA;5. Department of Neuroscience, University of Rochester Medical Center, USA |
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| Abstract: | Nicotinic acid (NA) and nicotinamide (NAM) are major forms of niacin and exert their physiological functions as precursors of nicotinamide adenine dinucleotide (NAD). Sirtuins, which are NAD-dependent deacetylases, regulate glucose and lipid metabolism and are implicated in the pathophysiology of aging, diabetes, and hepatic steatosis. The aim of this study was to investigate the effects of two NAD donors, NA and NAM, on glucose metabolism and the hepatic NAD-sirtuin pathway. The effects were investigated in OLETF rats, a rodent model of obesity and type 2 diabetes. OLETF rats were divided into five groups: (1) high fat (HF) diet, (2) HF diet and 10 mg NA/kg body weight (BW)/day (NA 10), (3) HF diet and 100 mg NA/kg BW/day (NA 100), (4) HF diet and 10 mg NAM/kg BW/day (NAM 10), and (5) HF diet and 100 mg NAM/kg BW/day (NAM 100). NA and NAM were delivered via drinking water for four weeks. NAM 100 treatment affected glucose control significantly, as shown by lower levels of accumulative area under the curve during oral glucose tolerance test, serum fasting glucose, serum fasting insulin, and homeostasis model assessment of insulin resistance, and higher levels of serum adiponectin. With regard to NAD-sirtuin pathway, intracellular nicotinamide phosphoribosyltransferase, NAD, the NAD/NADH ratio, Sirt1, 2, 3, and 6 mRNA expressions, and Sirt1 activity all increased in livers of NAM 100-treated rats. These alterations were accompanied by the increased levels of proliferator-activated receptor gamma, coactivator 1 alpha and mitochondrial DNA. The effect of NA treatment was less evident than that of NAM 100. These results demonstrate that NAM is more effective than NA on the regulation of glucose metabolism and the NAD-sirtuin pathway, which may relate to the altered mitochondrial biogenesis. |
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