title: Upregulation of IRS-1 expression in Goto-Kakizaki rats following Roux-en-Y gastric bypass surgery: resolution of type 2 diabetes?
abstract: Type 2 diabetes mellitus (T2DM) is an endocrine disorder that is rapidly growing in prevalence within China and throughout the world. Roux-en-Y gastric bypass (RYGB) surgery, widely used in the treatment of obesity, has been recognized as an effective and long-term treatment for T2DM in recent years. However, the underlying mechanisms responsible for glycemic control remain unclear. This study was designed to investigate the roles of insulin receptor substrates (IRSs) in glucose tolerance and insulin resistance following RYGB surgery. Goto-Kakizaki (GK) rats, a model of T2DM, were randomly allocated into three groups: RYGB surgery, sham surgery, and control (10 animals/group). Wistar rats were also used as non-diabetic control. Daily food intake, body weight, glucose and insulin were measured pre- and post-operatively. Insulin receptor substrate 1 (IRS-1) and insulin receptor substrate 2 (IRS-2) content, the main subtypes of IRSs, were measured in skeletal muscle, adipose tissue and liver using western immunoblot analyses on postoperative day 28. Following surgery, RYGB-treated rats showed markedly improved oral glucose tolerance, as judged by lower peak and area-under-the-curve glucose values (p < 0.01 vs. GK or GK sham). Improved insulin resistance was also observed in RYGB-treated rats. Western immunoblot analyses showed that IRS-1 and its phosphorylation levels were significantly increased in skeletal muscle and adipose tissues in RYGB group (p < 0.01 vs. GK or GK sham), whereas IRS-2 levels were downregulated in liver. These findings suggest that improvements in glucose tolerance and insulin resistance following RYGB surgery are associated with upregulation of IRS-1.
authors: Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, PR China.
authors: Shu-Qiang
authors: SQ
authors: Li
authors: Yong
authors: Y
authors: Zhou
authors: Yong
authors: Y
authors: Wang
authors: Yuan
authors: Y
authors: Liu
authors: Dong-Hua
authors: DH
authors: Geng
authors: Jin-Gang
authors: JG
authors: Liu
mesh_terms: D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000601:surgery*; D015390:Gastric Bypass; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D009928:Organ Specificity; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat