a combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic goto–kakizaki rats结合营养改善骨骼肌线粒体生物起源和函数2型糖尿病goto-kakizaki老鼠.pdfVIP

A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats 1 1,2 1,2 1 1 1,2 1 Weili Shen , Jiejie Hao , Chuan Tian , Jinmin Ren , Lu Yang , Xuesen Li , Cheng Luo , Carl W. 3 3 Cotma , Jiankang Liu * 1 Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China, 2 Graduate School of the Chinese Academy of Sciences, Beijing, China, 3 Institute for Brain Aging and Dementia, University of California Irvine, Irvine, California, United States of America Abstract Background: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto–Kakizaki rats. Methodology/Principal Findings: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-a-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved i