The lack of 5-adrenoceptors results in enhanced insulin sensitivity in mice exhibiting increased adiposity and glucose intolerance
The lack of 5-adrenoceptors results in enhanced insulin sensitivity in mice exhibiting increased adiposity and glucose intolerance
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DOI：
10.2337/diabetes.54.12.3490
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发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Muzzin, P
中科院分区：
文献类型：
--
作者：
Asensio, C;Jimenez, M;Muzzin, P
我们和其他人之前已经证明，缺乏β（1）/β（2）/β（3）肾上腺素受体的三重基因敲除小鼠（β-less小鼠）在成年后会出现进行性肥胖。在这里，我们研究了肥胖发生前无β小鼠的葡萄糖稳态。我们发现，β-less 小鼠的脂肪量增加，并且葡萄糖不耐受。此外，我们观察到，β-less 小鼠的葡萄糖诱导的胰岛素分泌受损，并且在进食状态下肝脏 PEPCK 基因表达增加，这表明它们的糖异生作用增加。尽管这些特征通常与胰岛素抵抗有关，但无β小鼠在胰岛素耐受测试中表现出增强的胰岛素敏感性。这与正常血糖-高胰岛素钳夹过程中获得的结果一致，表明无β小鼠表现出胰岛素反应性增加，同时肝葡萄糖产生受到正常抑制。总而言之，我们的结果表明，需要完整的β-肾上腺素能系统来调节整体葡萄糖稳态，特别是胰岛素介导的葡萄糖摄取，最有可能在肌肉和脂肪组织水平。
We and others have previously shown that triple knockout mice lacking the beta(1)/beta(2)/beta(3)-adrenoceptors (beta-less mice) developed a progressive obesity at adulthood. Here, we studied the glucose homeostasis in beta-less mice before the onset of obesity. We show that beta-less mice have increased fat mass and are glucose intolerant. In addition, we observed that beta-less mice have impaired gldcose-induced insulin secretion and exhibit an increase in, liver PEPCK gene expression in the fed state, suggesting that they have increased gluconeogenesis. Although these characteristics are usually associated with insulin resistance, beta-less mice exhibit enhanced insulin sensitivity during insulin tolerance tests. This is keeping with the results obtained during euglycemic-hyperinsulinemic clamps showing that beta-less mice display increased insulin responsiveness with normal suppression of hepatic glucose production. Altogether, our results suggest that an intact beta-adrenergic system is required to regulate overall glucose homeostasis and, in particular, insulin-mediated glucose uptake, most likely at the level of muscles and adipose tissue.