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

2019-03-07T14:42:50Z (GMT) by Kai Zou Joseph Houmard
<div><h4>BACKGROUND: </h4><p>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<sup>2</sup>), 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.</p><h4>OBJECTIVES: </h4><p>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.</p><h4>SETTING: </h4><p>East Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute.</p><h4>METHODS: </h4><p>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.</p><h4>RESULTS: </h4><p>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%).</p><h4>CONCLUSION: </h4><p>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.</p></div>