Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients
Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients
复制标题
DOI：
10.1007/s00125-004-1394-7
复制
发表时间：
2004-05-01
期刊：
影响因子：
8.2
通讯作者：
Vidal, H
中科院分区：
文献类型：
--
作者：
Debard, C;Laville, M;Vidal, H
目标/假设。长链脂肪酸氧化缺陷是胰岛素抵抗和 2 型糖尿病的一个特征。我们的目的是比较健康受试者和 2 型糖尿病患者骨骼肌中编码该途径主要蛋白质和酶的基因的表达水平。方法。在健康瘦受试者和患有明显 2 型糖尿病的胰岛素抵抗肥胖患者中，在 3 小时高胰岛素正常血糖钳夹之前和结束时进行骨骼肌活检，使用实时 PCR 对 16 个基因的基础和胰岛素调节 mRNA 浓度进行定量。糖尿病患者肌肉中乙酰辅酶A羧化酶2 mRNA表达增加了2.5倍。糖尿病患者中肉碱棕榈酰转移酶-1、两种脂联素受体以及参与脂肪酸转运和激活的基因的表达没有改变。高胰岛素血症持续3小时会增加多种脂肪酸氧化基因的表达，包括脂联素受体1和过氧化物酶体增殖物激活受体γ辅激活物1α。它还降低了丙酮酸脱氢酶 4 mRNA 水平。胰岛素对 2 型糖尿病患者肌肉中除脂联素受体 1 和丙酮酸脱氢酶 4 mRNA 之外的基因表达的影响显着改变。结论/解释。 2 型糖尿病患者肌肉中脂联素受体的表达没有改变。观察到的乙酰辅酶A羧化酶2的过度表达与2型糖尿病中骨骼肌丙二酰辅酶A浓度增加可能有助于抑制长链脂肪酸氧化的假设是一致的。
Aims/hypothesis. Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients.Methods. The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR in skeletal muscle biopsies taken before and at the end of a 3-hour hyperinsulinaemic-euglycaemic clamp in healthy lean subjects and in insulin-resistant obese patients with manifest Type 2 diabetes.Results. Acetyl CoA carboxylase-2 mRNA expression was increased 2.5-fold in the muscle of the diabetic patients. The expression of carnitine palmitoyl transferase-1, of the two adiponectin receptors and of genes involved in fatty acid transport and activation was not altered in diabetic patients. Hyperinsulinaemia for 3 hours increased the expression of several genes of fatty acid oxidation, including adiponectin receptor-1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha. It also reduced pyruvate dehydrogenase 4 mRNA levels. The effects of insulin on gene expression were markedly altered in the muscle of Type 2 diabetic patients except for adiponectin receptor-1 and pyruvate dehydrogenase 4 mRNAs.Conclusions/interpretation. The expression of adiponectin receptors was not altered in the muscle of Type 2 diabetic patients. The observed overexpression of acetyl CoA carboxylase-2 is consistent with the hypothesis that increased skeletal muscle malonyl CoA concentrations in Type 2 diabetes may contribute to the inhibition of long-chain fatty acid oxidation.