Influence of PPAR-α agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes
Influence of PPAR-α agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes
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DOI：
10.33549/physiolres.931058
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发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Haluzik, M.
中科院分区：
文献类型：
--
作者：
Anderlova, K.;Dolezalova, R.;Haluzik, M.
PPAR-α 激动剂可改善肥胖/胰岛素抵抗啮齿动物模型中的胰岛素敏感性，但其对人类胰岛素敏感性的影响尚不清楚。我们通过高胰岛素等血糖钳夹测量了 10 名患有 2 型糖尿病的肥胖女性在使用 PPAR-α 激动剂非诺贝特治疗三个月之前和之后的胰岛素敏感性，并研究了脂肪组织内分泌功能的变化在非诺贝特代谢作用中的可能作用。基线时，患有 2 型糖尿病的肥胖女性的体重指数、血清葡萄糖、甘油三酯、糖化血红蛋白和致动脉粥样硬化指数显着升高，而血清 HDL 胆固醇和脂联素浓度显着低于对照组 (n=10)。肥胖组和对照组之间血清抵抗素水平没有差异。非诺贝特治疗降低了血清甘油三酯浓度，而服用非诺贝特三个月后血糖和糖化血红蛋白均升高。非诺贝特治疗对血清脂联素或抵抗素浓度没有显着影响。与治疗前的对照组相比，肥胖糖尿病组中通过高胰岛素等血糖钳测量测量的所有胰岛素敏感性参数均显着降低，并且不受非诺贝特给药的影响。我们的结论是，服用 PPAR-α 激动剂非诺贝特三个月不会显着影响肥胖 2 型糖尿病受试者的胰岛素敏感性或抵抗素和脂联素浓度。与啮齿类动物相比，非诺贝特对人类缺乏胰岛素增敏作用，可能是由于人类肝脏和肌肉中 PPAR-α 的表达普遍较低。
PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.