Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat.
Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat.
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DOI：
10.1097/sla.0b013e3181904af0
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发表时间：
2009-02
影响因子：
9
通讯作者：
Cooney RN
中科院分区：
文献类型：
--
作者：
Meirelles K;Ahmed T;Culnan DM;Lynch CJ;Lang CH;Cooney RN
肥胖相关糖尿病是由胰岛素抵抗和β细胞功能障碍引起的。目前的研究探讨了食物摄入量、体重减轻、体脂库、耗氧量、胰岛素敏感性和肠促胰岛素水平的变化，作为 Roux-en-Y 胃绕道手术 (RYGB) 后改善糖耐量的潜在机制。研究人员对三组遗传性肥胖 Zucker 大鼠进行了研究：RYGB、假手术配对喂养 (PF) 和假手术随意喂养 (AL) 喂养的大鼠。测量体重、内脏和皮下脂肪库、口服葡萄糖耐量、胰岛素敏感性以及胰岛素、胰高血糖素、胰高血糖素样肽-1 (GLP-1)、葡萄糖依赖性促胰岛素肽和肽 YY (PYY) 的血浆浓度的变化。与 PF 和 AL 组相比，RYGB 后体重和皮下脂肪均减少。 RYGB 后内脏脂肪的减少主要是由于食物限制。仅 RYGB 组的葡萄糖耐量和胰岛素敏感性显着改善（与 AL、PF 相比，P <0.05）。正常血糖、高胰岛素钳夹研究表明 RYGB 改善了胰岛素刺激外周（例如骨骼肌）葡萄糖摄取的能力。各组之间的空腹总 GLP-1、葡萄糖依赖性促胰岛素肽和 PYY 水平相似，而与 PF 和 AL 对照组相比，RYGB 组中完整 GLP-1 (7-36) 酰胺、总 GLP-1 和 PYY 的餐后血浆水平升高。 RYGB 后的血糖稳态与皮下脂肪减少、餐后 PYY、GLP-1 和胰岛素增加以及胰岛素敏感性/作用改善相关。食物摄入量和内脏脂肪的变化似乎并不能解释 Zucker 大鼠模型中 RYGB 后胰岛素作用的改善。
Obesity-related diabetes is caused by insulin resistance and β-cell dysfunction. The current study examines changes in food intake, weight loss, body fat depots, oxygen consumption, insulin sensitivity, and incretin levels as potential mechanisms for improved glucose tolerance after Roux-en-Y gastric bypass (RYGB). Three groups of genetically obese Zucker rats were studied: RYGB, sham surgery pair-fed (PF), and sham surgery ad libitum (AL) fed rats. Changes in body weight, visceral and subcutaneous fat depots, oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide, and peptide YY (PYY) were measured. Body weight and subcutaneous fat were decreased after RYGB, compared with the PF and AL groups. The reduction in visceral fat after RYGB appeared largely because of food restriction. Glucose tolerance and insulin sensitivity were significantly improved in only the RYGB group (P <0.05 vs. AL, PF). Euglycemic, hyperinsulinemic clamp studies indicated RYGB improved the ability of insulin to stimulate peripheral (eg, skeletal muscle) glucose uptake. Fasting total GLP-1, glucose-dependent insulinotropic peptide, and PYY levels were similar between the groups, whereas postprandial plasma levels of intact GLP-1 (7–36) amide, total GLP-1, and PYY were increased in the RYGB group compared with PF and AL controls. Glucose homeostasis after RYGB is associated with decreased subcutaneous fat, increased postprandial PYY, GLP-1, and insulin, as well as improved insulin sensitivity/action. Changes in food intake and visceral fat do not seem to explain improvements in insulin action after RYGB in the Zucker rat model.