Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.
Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.
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DOI：
10.2337/dc09-0684
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发表时间：
2009-08
期刊：
影响因子：
16.2
通讯作者：
Tripathy D
中科院分区：
文献类型：
--
作者：
Chavez AO;Molina-Carrion M;Abdul-Ghani MA;Folli F;Defronzo RA;Tripathy D
成纤维细胞生长因子（FGF）-21在啮齿类动物的肝脏中高度表达并调节肝脏葡萄糖产生和脂质代谢。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，并研究其与胰岛素敏感性的关系，在不同程度的肥胖和糖耐量受试者。41例受试者（8例瘦型糖耐量正常[NGT]，9例肥胖型糖耐量正常[NGT]，12例空腹血糖受损[IFG]/糖耐量受损[IGT]，12例2型糖尿病受试者）接受口服葡萄糖耐量试验（OGTT）和高胰岛素-正葡萄糖钳夹（80 mU/m2/min）联合3-[3 H]葡萄糖输注。与瘦的NGT受试者相比，2型糖尿病受试者、IGT受试者和NGT肥胖受试者存在胰岛素抵抗。血浆FGF-21水平从患有NGT的瘦型受试者的3.9 ± 0.3 ng/ml逐渐增加至患有NGT的肥胖受试者的4.9 ± 0.2 ng/ml、患有IGT的受试者的5.2 ± 0.2 ng/ml和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水平也与空腹血糖[r = 0.312，P = 0.05]、2小时血糖[r = 0.414，P = 0.01]和A1 C [r = 0.325，P = 0.04]相关。血浆FGF-21水平在胰岛素抵抗状态下增加，并与肝脏和全身（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发挥作用。
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. 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/m2 per min) combined with 3-[3H] glucose infusion. 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]). 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.
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影响因子：
--
作者：
STEELE, R;WALL, JS;ALTSZULER, N
通讯作者：
ALTSZULER, N
正常受试者和新诊断 2 型糖尿病患者的循环 FGF-21 水平
影响因子：
1.8
作者：
Chen, W. -W.;Li, L.;Boden, G.
通讯作者：
Boden, G.
2 型糖尿病酮症患者血浆 FGF-21 水平
影响因子：
5.1
作者：
Li, Ling;Yang, Gangyi;Chen, Wenwen
通讯作者：
Chen, Wenwen
影响因子：
5.6
作者：
Kharitonenkov, Alexei;Dunbar, James D.;Shanafelt, Armen B.
通讯作者：
Shanafelt, Armen B.
影响因子：
5.3
作者：
Goetz, Regina;Beenken, Andrew;Mohammadi, Moosa
通讯作者：
Mohammadi, Moosa