PMID- 33952301 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210509 IS - 1743-7075 (Print) IS - 1743-7075 (Electronic) IS - 1743-7075 (Linking) VI - 18 IP - 1 DP - 2021 May 5 TI - Protective effects of calorie restriction on insulin resistance and islet function in STZ-induced type 2 diabetes rats. PG - 48 LID - 10.1186/s12986-021-00575-y [doi] LID - 48 AB - BACKGROUND: Caloric 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. METHODS: Sixty 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. RESULTS: We 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. CONCLUSION: CR (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. FAU - Zhang, Li AU - Zhang L AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. AD - Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 518100, China. FAU - Huang, Ying-Juan AU - Huang YJ AD - Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 518100, China. FAU - Sun, Jia-Pan AU - Sun JP AD - Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 518100, China. FAU - Zhang, Ting-Ying AU - Zhang TY AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Liu, Tao-Li AU - Liu TL AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Ke, Bin AU - Ke B AD - Department of VIP Ward, Sun Yat-Sen University Cancer Center, Guangzhou, 510080, China. FAU - Shi, Xian-Fang AU - Shi XF AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Li, Hui AU - Li H AD - Department of Obese and Metabolic Disease, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, 511400, China. FAU - Zhang, Geng-Peng AU - Zhang GP AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Ye, Zhi-Yu AU - Ye ZY AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Hu, Jianguo AU - Hu J AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. FAU - Qin, Jian AU - Qin J AUID- ORCID: 0000-0001-5877-8315 AD - Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China. himybox@yeah.net. LA - eng GR - 81874498/National Natural Science Foundation of China/ GR - SZLY2018002/Shenzhen Healthcare Research Project/ GR - 201903010044/Science and Technology Program of Guangzhou/ GR - GM2019020022/Traditional Chinese Medicine Research Project of Guangming District/ PT - Journal Article DEP - 20210505 PL - England TA - Nutr Metab (Lond) JT - Nutrition & metabolism JID - 101231644 PMC - PMC8097947 OTO - NOTNLM OT - AKT /AS160/GLUT4 OT - Calorie restriction OT - Diabetes OT - Insulin resistance OT - Streptozotocin COIS- The authors declare that they have no competing interests. EDAT- 2021/05/07 06:00 MHDA- 2021/05/07 06:01 PMCR- 2021/05/05 CRDT- 2021/05/06 05:46 PHST- 2020/10/10 00:00 [received] PHST- 2021/04/16 00:00 [accepted] PHST- 2021/05/06 05:46 [entrez] PHST- 2021/05/07 06:00 [pubmed] PHST- 2021/05/07 06:01 [medline] PHST- 2021/05/05 00:00 [pmc-release] AID - 10.1186/s12986-021-00575-y [pii] AID - 575 [pii] AID - 10.1186/s12986-021-00575-y [doi] PST - epublish SO - Nutr Metab (Lond). 2021 May 5;18(1):48. doi: 10.1186/s12986-021-00575-y.