Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA; Laboratory of Biological Nutrition EA2498, University Paris-Descartes, Faculty of Pharmacy, Paris, France.
Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA.
Nutrition. 2011 Jan;27(1):73-80. doi: 10.1016/j.nut.2010.08.005.
In the severely obese, Roux-en-Y gastric bypass (RYGB) reverses diabetes before body weight loss occurs. We determined changes in protein expression of insulin receptor (IR), its substrates (IRS1 and IRS2), and their phosphorylated state (p-IR and p-IRS1/2) in skeletal muscle (SM), liver and adipose tissue (AT), and GLUT4 in SM and AT, 14 and 28 d after RYGB to gaining insight into the time-related dynamics of insulin transduction pathway that may contribute to diabetes resolution.
RYGB induces a rapid weight loss followed by a slower weight loss period, leading to reversal of diabetes. We hypothesize that diabetes reversal is due to RYGB-induced up-regulation of insulin signaling pathway.
Diet-induced obese rats had RYGB or sham-operation (obese-controls). Daily food intake, body weight, glucose, insulin, and adiponectin were measured. IR, IRS1, IRS2, p-IR, and p-IRS1/2 were measured in SM, liver, and AT and GLUT4 in SM and AT, 14 and 28 d after RYGB, respectively, reflecting the rapid and slower weight loss periods after RYGB.
On day 14, in RYGB rats versus obese-controls, food intake, body weight, and fat mass decreased. Rats became normo-glycemic and had low insulin levels and elevated glucose:insulin ratio and decreased adiponectin concentrations. This persisted to day 28, except that adiponectin rose. No change in IR occurred on day 14, in RYGB rats versus obese-controls. By day 28 RYGB rats had a higher IR expression in SM and liver, but no changes in AT. RYGB induced a time-related increase in p-IR in liver and in pIRS1/2 in SM and liver. An increase in GLUT4 occurred by day 28 in SM and AT.
Improvement in diabetes occurred after RYGB due to up-regulation in key insulin pathway proteins at several levels, predominantly in SM and liver in association with ongoing caloric restriction, body weight, and fat mass loss.
在严重肥胖的患者中，胃旁路术（RYGB）在体重减轻之前逆转糖尿病。我们测定了 RYGB 后 14 天和 28 天骨骼肌（SM）、肝脏和脂肪组织（AT）中胰岛素受体（IR）、其底物（IRS1 和 IRS2）及其磷酸化状态（p-IR 和 p-IRS1/2）以及 SM 和 AT 中 GLUT4 的蛋白表达变化，以深入了解可能有助于糖尿病缓解的胰岛素转导途径的时间相关动力学。
RYGB 导致快速的体重减轻，随后是较慢的体重减轻阶段，从而逆转糖尿病。我们假设糖尿病的逆转是由于 RYGB 诱导胰岛素信号通路的上调。
饮食诱导肥胖大鼠接受 RYGB 或假手术（肥胖对照组）。每天测量食物摄入量、体重、血糖、胰岛素和脂联素。RYGB 后 14 天和 28 天分别测量 SM、肝脏和 AT 中的 IR、IRS1、IRS2、p-IR 和 p-IRS1/2，以及 SM 和 AT 中的 GLUT4，反映 RYGB 后快速和较慢的体重减轻阶段。
在 RYGB 大鼠与肥胖对照组相比，第 14 天，食物摄入量、体重和脂肪量减少。大鼠血糖正常，胰岛素水平较低，血糖：胰岛素比值升高，脂联素浓度降低。这一情况持续到第 28 天，除了脂联素升高。第 14 天，RYGB 大鼠与肥胖对照组相比，IR 没有变化。到第 28 天，RYGB 大鼠的 SM 和肝脏中 IR 表达增加，但 AT 没有变化。RYGB 诱导了肝中 p-IR 和 SM 和肝中 pIRS1/2 的时间相关增加。第 28 天，SM 和 AT 中的 GLUT4 增加。
RYGB 后糖尿病的改善是由于几个水平的关键胰岛素途径蛋白的上调所致，主要在 SM 和肝脏中，与持续的热量限制、体重和脂肪量减轻有关。
