Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 77030, USA.
J Clin Endocrinol Metab. 2010 Apr;95(4):1916-23. doi: 10.1210/jc.2009-0911. Epub 2010 Feb 15.
Lipotoxicity (increased tissue fat content) has been implicated in the development of muscle insulin resistance and type 2 diabetes mellitus (T2DM).
The aim was to study the effect of pioglitazone on intramyocellular fat metabolism.
Twenty-four T2DM subjects (glycosylated hemoglobin = 8.3 +/- 0.4%) participated in three similar study protocols before and after 4 months of 45 mg/d pioglitazone treatment: 1) 3-h euglycemic insulin (80 mU/m(2) . min) clamp with measurement of intramyocellular fat with proton nuclear magnetic resonance; 2) vastus lateralis muscle biopsy for measurement of LC-FACoAs 60 min before start of the insulin clamp; and 3) muscle biopsy for measurement of diacylglycerol 60 min before start of the insulin clamp.
In all three protocols, pioglitazone similarly reduced (all P < 0.05) the glycosylated hemoglobin (Delta = 0.8-1.2%), fasting plasma glucose (39-76 mg/dl), fasting free fatty acid (132-236 mumol/liter), and increased insulin-stimulated glucose disposal (by 25-56%). Intramyocellular fat (protocol I) declined from 1.5 to 0.9% (P < 0.05) and correlated with the increase in glucose disposal rate (r = 0.65; P < 0.05). Long chain-fatty acyl-coenzyme A decreased from 12.5 to 8.1 nmol/g (P < 0.05) and correlated with the increase in disposal rate (r = 0.76; P < 0.05). Pioglitazone therapy had no effect on muscle diacylglycerol content.
Pioglitazone improves insulin resistance in T2DM in association with mobilization of fat and toxic lipid metabolites out of muscle.
脂毒性（组织脂肪含量增加）与肌肉胰岛素抵抗和 2 型糖尿病（T2DM）的发生有关。
研究吡格列酮对肌内脂肪代谢的影响。
24 例 T2DM 患者（糖化血红蛋白=8.3±0.4%）在接受 4 个月 45mg/d 吡格列酮治疗前后参加了三个类似的研究方案：1）3 小时血糖正常胰岛素（80mU/m2·min）钳夹，用质子磁共振测量肌内脂肪；2）在胰岛素钳夹开始前 60 分钟测量股外侧肌活检中的 LC-FACoAs；3）在胰岛素钳夹开始前 60 分钟进行肌肉活检，测量二酰基甘油。
在所有三个方案中，吡格列酮均相似地降低（均 P＜0.05）糖化血红蛋白（Delta=0.8-1.2%）、空腹血糖（39-76mg/dl）、空腹游离脂肪酸（132-236μmol/L）和增加胰岛素刺激的葡萄糖摄取（增加 25-56%）。肌内脂肪（方案 I）从 1.5%降至 0.9%（P＜0.05），与葡萄糖摄取率的增加呈正相关（r=0.65；P＜0.05）。长链脂肪酸辅酶 A 从 12.5 降至 8.1nmol/g（P＜0.05），与摄取率的增加呈正相关（r=0.76；P＜0.05）。吡格列酮治疗对肌肉二酰基甘油含量没有影响。
吡格列酮改善 T2DM 患者的胰岛素抵抗，与脂肪和毒性脂质代谢产物从肌肉中动员有关。
