Boden Guenther, Homko Carol, Mozzoli Maria, Showe Louise C, Nichols Calen, Cheung Peter
Division of Endocrinology, Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, PA, USA.
Diabetes. 2005 Mar;54(3):880-5. doi: 10.2337/diabetes.54.3.880.
Thiazolidinediones (TZDs) are a new class of insulin-sensitizing drugs. To explore how and in which tissues they improve insulin action, we obtained fat and muscle biopsies from eight patients with type 2 diabetes before and 2 months after treatment with rosiglitazone (n = 5) or troglitazone (n = 3). TZD treatment was associated with a coordinated upregulation in the expression of genes and synthesis of proteins involved in fatty acid uptake, binding, beta-oxidation and electron transport, and oxidative phosphorylation in subcutaneous fat but not in skeletal muscle. These changes were accompanied by a 13% increase in total body fat oxidation, a 20% decrease in plasma free fatty acid levels, and a 46% increase in insulin-stimulated glucose uptake. We conclude that TZDs induced a coordinated stimulation of fatty acid uptake, oxidation, and oxidative phosphorylation in fat of diabetic patients and thus may have corrected, at least partially, a recently recognized defect in patients with type 2 diabetes consisting of reduced expression of genes related to oxidative metabolism and mitochondrial function.
噻唑烷二酮类药物（TZDs）是一类新型的胰岛素增敏药物。为了探究它们如何以及在哪些组织中改善胰岛素作用，我们在8例2型糖尿病患者接受罗格列酮（n = 5）或曲格列酮（n = 3）治疗前及治疗2个月后获取了脂肪和肌肉活检样本。TZDs治疗与皮下脂肪中参与脂肪酸摄取、结合、β氧化、电子传递以及氧化磷酸化的基因表达上调和蛋白质合成协调增加有关，而在骨骼肌中未出现这种情况。这些变化伴随着全身脂肪氧化增加13%、血浆游离脂肪酸水平降低20%以及胰岛素刺激的葡萄糖摄取增加46%。我们得出结论，TZDs可诱导糖尿病患者脂肪中脂肪酸摄取、氧化及氧化磷酸化的协调刺激，因此可能至少部分纠正了2型糖尿病患者最近被认识到的一种缺陷，该缺陷包括与氧化代谢和线粒体功能相关基因的表达降低。
