Protective effects of calorie restriction on insulin resistance and islet function in STZ-induced type 2 diabetes rats

Nutrition & Metabolism

Hui Li¹  Ying-juan Huang²  Jia-pan Sun²  Zhi-yu Ye³  Ting-ying Zhang³  Geng-peng Zhang³  Jian Qin³  Jianguo Hu³  Xian-fang Shi³  Tao-li Liu³  Li Zhang⁴  Bin Ke⁵ 

[1] Department of Obese and Metabolic Disease, Guangzhou Panyu Hospital of Chinese Medicine, 511400, Guangzhou, China;Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, 518100, Guangzhou, China;Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, 518107, Shenzhen, China;Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, 518107, Shenzhen, China;Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, 518100, Guangzhou, China;Department of VIP Ward, Sun Yat-Sen University Cancer Center, 510080, Guangzhou, China;

关键词: Calorie restriction;    Diabetes;    Insulin resistance;    Streptozotocin;    AKT /AS160/GLUT4;   

DOI  :  10.1186/s12986-021-00575-y

来源: Springer

【 摘 要 】

BackgroundCaloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms.MethodsSixty male Sprague–Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling.ResultsWe found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR.ConclusionCR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

【 授权许可】

CC BY