Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin - Evidence from cultured myotubes
Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin - Evidence from cultured myotubes
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DOI：
10.2337/diabetes.53.3.542
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Beck-Nielsen, H
中科院分区：
文献类型：
--
作者：
Gaster, M;Rustan, AC;Beck-Nielsen, H
体内骨骼肌胰岛素抵抗与脂质氧化和脂质积累减少有关。脂质代谢的变化是否代表细胞水平上的适应性补偿或遗传性状的直接表达仍不确定。从对照组和2型糖尿病患者建立的人肌管中棕榈酸盐代谢的研究可能解决这个问题，因为遗传缺陷在体外被保存和表达。在这项研究中，在基础条件和急性胰岛素刺激下，对照组和2型糖尿病患者建立的肌管中棕榈酸的总摄取是相似的。与基础条件下的对照肌管相比，糖尿病患者的肌管表现出初级减少的棕榈酸氧化为二氧化碳，同时棕榈酸转化为磷脂的酯化反应增加。三酰基甘油（TAG）含量和棕榈酸掺入二酰基甘油（DAG）和TAG的基本条件下各组之间没有变化。急性胰岛素治疗显著增加了两个研究组建立的肌管中棕榈酸的摄取和棕榈酸并入DAG和TAG，但在对照组和糖尿病受试者建立的肌管中没有发现差异。这些结果提示，糖尿病骨骼肌体内脂质氧化降低可能具有遗传原因；在基础生理条件下，糖尿病肌肉中的TAG代谢似乎并不主要受到影响。
Insulin resistance in skeletal muscle in vivo is associated with reduced lipid oxidation and lipid accumulation. It is still uncertain whether changes in lipid metabolism represent an adaptive compensation at the cellular level or a direct expression of a genetic trait. Studies of palmitate metabolism in human myotubes established from control and type 2 diabetic subjects may solve this problem, as genetic defects are preserved and expressed in vitro. In this study, total uptake of palmitic acid was similar in myotubes established from both control and type 2 diabetic subjects under basal conditions and acute insulin stimulation. Myotubes established from diabetic subjects expressed a primary reduced palmitic acid oxidation to carbon dioxide with a concomitantly increased esterification of palmitic acid into phospholipids compared with control myotubes under basal conditions. Triacylglycerol (TAG) content and the incorporation of palmitic acid into diacylglycerol (DAG) and TAG at basal conditions did not vary between the groups. Acute insulin treatment significantly increased palmitate uptake and incorporation of palmitic acid into DAG and TAG in myotubes established from both study groups, but no difference was found in myotubes established from control and diabetic subjects. These results indicate that the reduced lipid oxidation in diabetic skeletal muscle in vivo may be of genetic origin; it also appears that TAG metabolism is not primarily affected in diabetic muscles under basal physiological conditions.