The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects
The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects
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DOI：
10.2337/diabetes.51.10.2968
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Olefsky, JM
中科院分区：
文献类型：
--
作者：
Yu, JG;Javorschi, S;Olefsky, JM
噻唑烷二酮类化合物的胰岛素增敏作用被认为是通过过氧化物酶体增殖物激活受体-γ介导的，这是一种在脂肪组织中高度丰富的核受体。据报道，脂肪细胞分泌多种蛋白质，包括肿瘤坏死因子-α、抵抗素、纤溶酶原激活物抑制物-1和脂联素。脂联素是一种脂肪细胞分泌的蛋白质，已被报道可增加脂肪氧化和改善胰岛素敏感性。我们的目的是研究曲格列酮对消瘦、肥胖和糖尿病受试者脂联素水平的影响。10名糖尿病受试者和17名非糖尿病受试者(瘦身8人，体重指数27 kg/m(2))参与研究。所有受试者都接受了80亩的检查。M(-2)。在TZD曲格列酮(TZD)600 mg/d治疗3个月前和治疗3个月后，分别出现高胰岛素-正常血糖钳夹(MIN-1)。糖尿病组治疗12周后空腹血糖较治疗前显著下降(9.1+/-0.9vs.11.1+/-0.9 mm ol/L，P<；0.005)，而瘦体和肥胖组无明显变化。治疗后全组空腹胰岛素水平明显低于治疗前(P=0.02)。在基线时，糖尿病受试者的葡萄糖处理率(R-d)较低(3.4+/-0.5 mg。Kg(-1)。M in(-1))明显高于瘦肉组(12.3±-0.4)和肥胖组(6.7+/-0.7)(P<；0.001)，糖尿病组和肥胖组治疗后均有显著改善(P<；0.05)，瘦肉组则无明显变化。基础脂联素水平糖尿病组显著低于消瘦组(9.0+/-1.7比16.7+/-2.7µg/ml，P=0.03)，治疗后均呈上升趋势(12.2+/-2.3比25.7+/-2.6µg/mlp<；10(-4))，三组间无显著差异。在葡萄糖钳夹期间，所有组的脂联素水平均低于基础水平(10.2+/-2.3比12.2+/-2.3微克/毫升，P<；0.01)。脂联素水平与R-d(r=0.46，P=0.016)、高密度脂蛋白(r=0.59，P<；0.001)呈正相关，与空腹胰岛素(r=-0.39，P=0.042)、甘油三酯(r=-0.61，P<；0.001)呈负相关。我们的发现表明，TZD治疗提高了所有受试者的脂联素水平，包括没有观察到TZD其他影响的正常受试者。胰岛素似乎也会抑制脂联素水平。我们已经在正常大鼠身上证实了这些结果。这些发现表明，脂联素可受肥胖、糖尿病、TZDS和胰岛素的调节，并可能在增强胰岛素敏感性方面发挥生理学作用。
The insulin-sensitizing effects of thiazolidinediones are thought to be mediated through peroxisome proliferator-activated receptor-gamma, a nuclear receptor that is highly abundant in adipose tissue. It has been reported that adipocytes secrete a variety of proteins, including tumor necrosis factor-alpha, resistin, plasminogen activator inhibitor-1, and adiponectin. Adiponectin is a fat cell-secreted protein that has been reported to increase fat oxidation and improve insulin sensitivity. Our aim was to study the effects of troglitazone on adiponectin levels in lean, obese, and diabetic subjects. Ten diabetic and 17 nondiabetic subjects (8 lean, BMI 27 kg/m(2)) participated in the study. All subjects'underwent an 80 mU . m(-2) . min(-1) hyperinsulinemic-euglycemic glucose clamp before and after 3 months' treatment with the thiazolidinedione (TZD) troglitazone (600 mg/day). Fasting plasma glucose significantly decreased in the diabetic group after 12 weeks of treatment compared with baseline (9.1 +/- 0.9 vs. 11.1 +/- 0.9 mmol/l, P < 0.005) but was unchanged in the lean and obese subjects. Fasting insulin for the entire group was significantly lower than baseline (P = 0.02) after treatment. At baseline, glucose disposal rate (R-d) was lower in the diabetic subjects (3.4 +/- 0.5 mg . kg(-1). min(-1)) than in the lean (12.3 +/- 0.4) or obese subjects (6.7 +/- 0.7) (P < 0.001 for both) and was significantly improved in the diabetic and obese groups (P < 0.05) after treatment, and it remained unchanged in the lean subjects. Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects (9.0 +/- 1.7 vs. 16.7 +/- 2.7 mug/ml, P = 0.03) and rose uniformly in all subjects (12.2 +/- 2.3 vs. 25.7 +/- 2.6 mug/ml p < 10(-4)) after treatment, with no significant difference detected among the three groups. During the glucose clamps, adiponectin levels were suppressed below basal levels in all groups (10.2 +/- 2.3 vs. 12.2 +/- 2.3 mug/ml, P < 0.01). Adiponectin levels correlated with R-d (r = 0.46, P = 0.016) and HDL cholesterol levels (r = 0.59, P < 0.001) and negatively correlated with fasting insulin (r = -0.39, P = 0.042) and plasma triglyceride (r = -0.61, P < 0.001). Our findings show that TZD treatment increased adiponectin levels in all subjects, including normal subjects in which no other effects of TZDs are observed. Insulin also appears to suppress adiponectin levels. We have confirmed these results in normal rats. These findings suggest that adiponectin can be regulated by obesity, diabetes, TZDs, and insulin, and it may play a physiologic role in enhancing insulin sensitivity.