Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys
Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys
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DOI：
10.2337/diabetes.50.5.1126
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发表时间：
2001-05-01
期刊：
影响因子：
7.7
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
脂联素是一种脂肪特异性血浆蛋白，其血浆浓度在肥胖受试者和2型糖尿病患者中降低。这种蛋白质具有公认的抗动脉粥样硬化和抗炎特性。在目前的研究中，我们分析了脂联素和胰岛素抵抗之间的关系，在恒河猴（猕猴），自发发展肥胖，随后经常进展为明显的2型糖尿病。肥胖和糖尿病猴的血浆脂联素水平与人类一样降低。前瞻性纵向研究显示，血浆脂联素水平在肥胖的早期阶段下降，并在2型糖尿病发展后持续下降。高胰岛素-正葡萄糖钳夹研究显示，血浆脂联素水平较低的肥胖猴表现出显著较低的胰岛素刺激外周葡萄糖摄取（M率）。血浆脂联素水平与M率呈显著正相关（r = 0.66，P < 0.001）。纵向上，血浆脂联素水平随着胰岛素抵抗的进展而降低。血浆脂联素水平与脂肪组织脂联素mRNA水平之间无明显相关性。这些结果表明，循环脂联素的减少可能与胰岛素抵抗的发展。
Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66,P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.