Chavez Alberto O, Molina-Carrion Marjorie, Abdul-Ghani Muhammad A, Folli Franco, Defronzo Ralph A, Tripathy Devjit
Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Diabetes Care. 2009 Aug;32(8):1542-6. doi: 10.2337/dc09-0684. Epub 2009 Jun 1.
OBJECTIVE Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m(2) per min) combined with 3-[(3)H] glucose infusion. RESULTS Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 +/- 0.3 ng/ml in lean subjects with NGT to 4.9 +/- 0.2 in obese subjects with NGT to 5.2 +/- 0.2 in subjects with IGT and to 5.3 +/- 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = -0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
目的 成纤维细胞生长因子（FGF）-21在肝脏中高表达，并调节啮齿动物的肝脏葡萄糖生成和脂质代谢。然而，其在人类2型糖尿病发病机制中的作用仍有待确定。本研究的目的是定量循环血浆FGF-21水平，并检查其与不同程度肥胖和糖耐量受试者胰岛素敏感性的关系。 研究设计与方法 41名受试者（8名糖耐量正常的瘦人、9名糖耐量正常的肥胖者、12名空腹血糖受损（IFG）/糖耐量受损（IGT）者和12名2型糖尿病受试者）接受了口服葡萄糖耐量试验（OGTT）和高胰岛素-正葡萄糖钳夹试验（每分钟80 mU/m²）并同时输注3-[(³)H]葡萄糖。 结果 与糖耐量正常的瘦人相比，2型糖尿病受试者、IGT受试者和糖耐量正常的肥胖受试者存在胰岛素抵抗。血浆FGF-21水平从糖耐量正常的瘦人的3.9±0.3 ng/ml逐渐升高至糖耐量正常的肥胖者的4.9±0.2 ng/ml、IGT受试者的5.2±0.2 ng/ml以及2型糖尿病受试者的5.3±0.2 ng/ml。FGF-21水平与全身（主要反映肌肉）胰岛素敏感性呈负相关（r = -0.421，P = 0.007），与肝脏胰岛素抵抗指数呈正相关（r = 0.344，P = 0.034）。FGF-21水平还与血糖指标相关（空腹血糖[r = 0.312，P = 0.05]、餐后2小时血糖[r = 0.414，P = 0.01]和糖化血红蛋白[r = 0.325，P = 0.04]）。 结论 胰岛素抵抗状态下血浆FGF-21水平升高，且与肝脏和全身（肌肉）胰岛素抵抗相关。FGF-21可能在2型糖尿病肝脏和全身胰岛素抵抗的发病机制中起作用。
