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胃旁路手术后非糖尿病严重肥胖人群的肌管中胰岛素作用的急性和慢性反应的差异。

Differential acute and chronic responses in insulin action in cultured myotubes following from nondiabetic severely obese humans following gastric bypass surgery.

机构信息

East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina; Department of Kinesiology, East Carolina University, Greenville, North Carolina; Human Performance Laboratory, East Carolina University, Greenville, North Carolina.

Department of Exercise and Health Sciences, University of Massachusetts Boston, Boston, Massachusetts.

出版信息

Surg Obes Relat Dis. 2017 Nov;13(11):1853-1862. doi: 10.1016/j.soard.2017.05.019. Epub 2017 May 26.

DOI:10.1016/j.soard.2017.05.019
PMID:28673470
Abstract

BACKGROUND

Roux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m), including improved peripheral insulin action. Although a major site of insulin action, the time course changes in skeletal muscle glucose metabolism following RYGB is unclear.

OBJECTIVES

To investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans.

SETTING

East Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute.

METHODS

Primary human skeletal muscle cells were isolated from biopsies obtained from 8 women with severe obesity before, 1 month, and 7 months following RYGB surgery. Glucose metabolism, glycogen content, and insulin signal transduction were determined in differentiated myotubes.

RESULTS

Insulin-stimulated glycogen synthesis and glucose oxidation increased in human myotubes derived from patients with severe obesity at both 1 and 7 months post-RYGB. However, there were no alterations indicative of enhanced insulin signal transduction. At 1 month post-RYGB, muscle glycogen levels were lower (-23%) and phosphorylation of acetyl CoA carboxylase 2 (ACC2) was elevated (+16%); both returned to presurgery levels at 7 months after RYGB in myotubes derived from patients. At 7 months post-RYGB, there was an increase in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein content (+54%).

CONCLUSION

These data indicate that insulin action intrinsically improves in cultured human primary myotubes derived from nondiabetic severely obese patients following RYGB surgery; however, the cellular alterations involved appear to consist of distinct acute and chronic components.

摘要

背景

Roux-en-Y 胃旁路(RYGB)手术已被证明可诱导严重肥胖(体重指数≥40kg/m)个体发生积极的代谢适应,包括改善外周胰岛素作用。尽管胰岛素作用的主要部位,但 RYGB 后骨骼肌葡萄糖代谢的时程变化尚不清楚。

目的

研究 RYGB 手术对源自非糖尿病严重肥胖个体的培养的人原代肌管中胰岛素刺激的葡萄糖代谢的急性和慢性影响。

设置

东卡罗莱纳大学减肥手术中心和东卡罗莱纳糖尿病和肥胖研究所。

方法

从 8 名严重肥胖女性接受 RYGB 手术前、1 个月和 7 个月获得的活检中分离出原代人骨骼肌细胞。在分化的肌管中测定葡萄糖代谢、糖原含量和胰岛素信号转导。

结果

源自严重肥胖患者的人肌管中胰岛素刺激的糖原合成和葡萄糖氧化在 RYGB 后 1 和 7 个月均增加。然而,没有提示增强胰岛素信号转导的改变。RYGB 后 1 个月,肌肉糖原水平降低(-23%),乙酰辅酶 A 羧化酶 2(ACC2)磷酸化升高(+16%);在 RYGB 后 7 个月,源自患者的肌管中均恢复到术前水平。RYGB 后 7 个月,过氧化物酶体增殖物激活受体γ共激活因子 1α(PGC1α)蛋白含量增加(+54%)。

结论

这些数据表明,源自非糖尿病严重肥胖患者的培养的人原代肌管中胰岛素作用内在改善;然而,所涉及的细胞改变似乎包括明显的急性和慢性成分。

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