Aim: The purpose of this study was to determine if intramyocellular glucose partitioning was altered in primary human myotubes derived from severely obese women with type 2 diabetes. Methods: Human skeletal muscle cells were obtained from lean non-diabetic and severely obese Caucasian females with type 2 diabetes (BMI: 23.6 ± 2.6 vs. 48.8 ± 1.9 kg/m², fasting glucose: 86.9 ± 1.6 vs. 135.6 ± 12.0 mg/dl, n=9/group). 1-[¹⁴C]-glucose metabolism (glycogen synthesis, glucose oxidation and non-oxidized glycolysis) and 1- and 2-[¹⁴C]-pyruvate oxidation were examined in fully differentiated myotubes under basal and insulin-stimulated conditions. Tricarboxylic acid cycle intermediates were determined via targeted metabolomics. Results: Myotubes derived from severely obese individuals with type 2 diabetes exhibited impaired insulin-mediated glucose partitioning with reduced rates of glycogen synthesis and glucose oxidation and increased rates of non-oxidized glycolytic products when compared to their non-diabetic counterparts (P < 0.05). Both 1- and 2-[¹⁴C]-pyruvate oxidation rates were significantly blunted in myotubes from severely obese women with type 2 diabetes in comparison to the non-diabetic controls. Lastly, tricarboxylic acid cycle intermediates citrate (P<0.05), cis-aconitic acid (P=0.07), and alpha-ketoglutarate (P<0.05) concentrations were lower in myotubes from severely obese women with type 2 diabetes. Conclusion: These data suggest that intramyocellular insulin-mediated glucose partitioning is intrinsically altered in the skeletal muscle of severely obese women with type 2 diabetes in a manner that favors the production of glycolytic end products. Defects in pyruvate dehydrogenase and tricarboxylic acid cycle may be responsible for this metabolic derangement associated with type 2 diabetes.

中文翻译：

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患有 2 型糖尿病的严重肥胖女性的原发性肌管中的葡萄糖分配受损。

目的：本研究的目的是确定来自患有 2 型糖尿病的严重肥胖女性的原代人肌管中肌细胞内葡萄糖分配是否发生改变。方法：从患有 2 型糖尿病（BMI：23.6 ± 2.6 vs. 48.8 ± 1.9 kg/m ²，空腹血糖：86.9 ± 1.6 vs. 135.6 ± 12.0 mg /dl，n=9/组）。1-[ ¹⁴ C]-葡萄糖代谢（糖原合成、葡萄糖氧化和非氧化糖酵解）和 1- 和 2-[ ¹⁴在基础和胰岛素刺激条件下，在完全分化的肌管中检查了 C]-丙酮酸氧化。三羧酸循环中间体通过靶向代谢组学确定。结果：与非糖尿病患者相比，来自严重肥胖的 2 型糖尿病患者的肌管表现出胰岛素介导的葡萄糖分配受损，糖原合成和葡萄糖氧化率降低，非氧化糖酵解产物率增加（P < 0.05） . 1- 和 2-[ ¹⁴与非糖尿病对照组相比，患有 2 型糖尿病的严重肥胖女性的肌管中的 C]-丙酮酸氧化率显着降低。最后，在患有 2 型糖尿病的严重肥胖女性的肌管中，三羧酸循环中间体柠檬酸盐 (P<0.05)、顺式乌头酸 (P=0.07) 和 α-酮戊二酸 (P<0.05) 浓度较低。结论：这些数据表明，肌细胞内胰岛素介导的葡萄糖分配在患有 2 型糖尿病的严重肥胖女性的骨骼肌中发生内在改变，其方式有利于糖酵解终产物的产生。丙酮酸脱氢酶和三羧酸循环的缺陷可能是造成这种与 2 型糖尿病相关的代谢紊乱的原因。