title: Resveratrol attenuates intermittent hypoxia-induced insulin resistance in rats: involvement of Sirtuin 1 and the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway.
abstract: Obstructive sleep apnea can induce chronic intermittent hypoxia (CIH) during sleep and is associated with obesity and diabetes. Resveratrol (RSV), a polyphenolic phytoalexin, can regulate glucose metabolism, thereby reducing insulin resistance. The present study aimed to assess whether RSV attenuates CIH-induced insulin resistance in rats and the underlying mechanisms. A total of 40 rats were randomly assigned into five groups: i) Control; ii) subjected to CIH only; iii) subjected to CIH and treated with 3 mg/kg/day of RSV; iv) subjected to CIH and treated with 30 mg/kg/day of RSV; v) subjected to CIH and treated with 60 mg/kg/day of RSV. All animals were sacrificed following 28 days of treatment. Subsequently, the blood and livers were harvested and blood insulin and glucose levels were measured. Levels of sirtuin (Sirt) 1, insulin receptor (InsR) and glucose transporter 2 (Glut2) in the liver were measured. RSV treatment was demonstrated to suppress weight gain and improve hepatic morphology. RSV treatment also significantly reduced the homeostasis model assessment estimate of insulin resistance of the rats exposed to CIH. This effect occurred in a dose-dependent manner. RSV significantly upregulated liver Sirt1 levels and inhibited InsR and Glut2 expression in the liver. Additionally, RSV activated the phosphorylation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and AKT. The present study demonstrates that RSV prevents CIH-induced insulin resistance in rats. Upregulation of Sirt1 and activation of PI3K/AKT signaling may be involved in this process.
authors.affiliation: Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Emergency Department, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Sun
authors.affiliation: Emergency Department, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Li
authors.affiliation: Emergency Department, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D020011:Protective Agents; D012333:RNA, Messenger; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D056564:Sirtuin 1; D000077185:Resveratrol