REGULATION OF THE LEVEL OF UNCOUPLING PROTEIN IN BROWN ADIPOSE-TISSUE BY INSULIN
REGULATION OF THE LEVEL OF UNCOUPLING PROTEIN IN BROWN ADIPOSE-TISSUE BY INSULIN
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DOI：
10.1152/ajpregu.1990.258.2.r418
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发表时间：
1990-02-01
影响因子：
--
通讯作者：
TRAYHURN, P
中科院分区：
文献类型：
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作者：
GELOEN, A;TRAYHURN, P
胰岛素在调节棕色脂肪组织（BAT）的产热活性和能力（解偶联蛋白含量）中的作用已经使用链脲佐菌素糖尿病小鼠进行了研究，然后输注不同剂量的胰岛素。糖尿病12天后，动物接受0、8、16或32单位的胰岛素。kg体重第-1天通过皮下植入渗透微型泵递送12天。糖尿病12天后，体重、肩胛间BAT和附睾白色脂肪组织重量均降低。在BAT中，线粒体蛋白质含量（63%）、细胞色素氧化酶活性（79%）、线粒体GDP结合（51%）以及解偶联蛋白的比线粒体浓度和总组织含量（分别为71%和89%）显著降低（P < 0.05），表明组织的产热活性和能力在糖尿病中降低。以8单位的剂量输注胰岛素。kg-1.第1天使线粒体GDP结合正常化，解偶联蛋白的浓度加倍。体重、附睾白色脂肪组织重量和BAT的线粒体蛋白质含量用16单位的胰岛素恢复。kg-1.第1天。更高剂量的胰岛素没有进一步增加解偶联蛋白的特定线粒体浓度，但BAT的线粒体含量（从而总解偶联蛋白含量）增加，血糖正常化。胰岛素替代剂量与线粒体蛋白含量（r = 0.68，P < 0.001）、细胞色素氧化酶活性（r = 0.54，P < 0.001）和总解偶联蛋白含量（r = 0.68，P < 0.001）相关。这些结果表明，胰岛素的外周水平调节BAT的解偶联蛋白含量，从而调节组织的产热能力。
The role of insulin in the regulation of the thermogenic activity and capacity (uncoupling protein content) of brown adipose tissue (BAT) has been investigated using mice made diabetic with streptozotocin and then subsequently infused with different doses of insulin. After 12 days of diabetes, the animals received either 0, 8, 16, or 32 units of insulin .cntdot. kg body wt-1 .cntdot. day-1 delivered by osmotic minipumps implanted subcutaneously for 12 days. After 12 days of diabetes, body weight, interscapular BAT, and epididymal white adipose tissue weights were each reduced. In BAT, significant decreases (P < 0.05) in the mitochondrial protein content (63%), cytochrome oxidase activity (79%), mitochondrial GDP binding (51%), and the specific mitochondrial concentration and total tissue content of uncoupling protein (71 and 89%, respectively) were obtained, indicating that the thermogenic activity and capacity of the tissue were reduced in diabetes. The infusion of insulin at a dose of 8 units .cntdot. kg-1 .cntdot. day-1 normalized mitochondrial GDP binding and doubled the concentration of uncoupling protein. Body weight, epididymal white adipose tissue weight, and the mitochondrial protein content of BAT were restored with 16 units of insulin .cntdot. kg-1 .cntdot. day-1. Higher doses of insulin did not further increase the specific mitochondrial concentration of uncoupling protein, but the mitochondrial content (and thereby the total uncoupling protein content) of BAT was increased and blood glucose normalized. There was a significant correlation between the dose of insulin replacement and several of the parameters measured in BAT: mitochondrial protein content (r = 0.68, P < 0.001), cytochrome oxidase activity (r = 0.54, P < 0.001), and total uncoupling protein content (r = 0.68, P < 0.001). These results indicate that the peripheral level of insulin regulates the uncoupling protein content of BAT and thus the thermogenic capacity of the tissue.