Fan W, Dinulescu D M, Butler A A, Zhou J, Marks D L, Cone R D
The Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Endocrinology. 2000 Sep;141(9):3072-9. doi: 10.1210/endo.141.9.7665.
The central melanocortin system has been demonstrated to play a pivotal role in energy homeostasis. Genetic disruption of this system causes obesity in both humans and mice. Previous experiments have shown that centrally-administered melanocortin agonists inhibit food intake and stimulate oxygen consumption. Here we report that centrally-administered melanocortin agonists also inhibit basal insulin release, and alter glucose tolerance. Furthermore, increased plasma insulin levels occur in the young lean MC4-R knockout (MC4-RKO) mouse, and impaired insulin tolerance takes place before the onset of detectable hyperphagia or obesity. These data suggest that the central melanocortin system regulates not only energy intake and expenditure, but also processes related to energy partitioning, as indicated by effects on insulin release and peripheral insulin responsiveness. Previous studies emphasize the role of excess adipose mass in the development of tissue insulin resistance, leading to type II diabetes. The data presented here show that defects in the central control of glucose homeostasis may be an additional factor in some types of obesity-associated type II diabetes.
中枢黑皮质素系统已被证明在能量平衡中起关键作用。该系统的基因破坏会导致人类和小鼠肥胖。先前的实验表明，中枢给予黑皮质素激动剂可抑制食物摄入并刺激氧气消耗。在此我们报告，中枢给予黑皮质素激动剂还可抑制基础胰岛素释放，并改变葡萄糖耐量。此外，年轻的瘦型MC4-R基因敲除（MC4-RKO）小鼠血浆胰岛素水平升高，并且在可检测到的食欲亢进或肥胖发作之前就出现了胰岛素耐受性受损。这些数据表明，中枢黑皮质素系统不仅调节能量摄入和消耗，还调节与能量分配相关的过程，如对胰岛素释放和外周胰岛素反应性的影响所示。先前的研究强调了过多脂肪量在组织胰岛素抵抗发展中的作用，进而导致II型糖尿病。此处呈现的数据表明，葡萄糖稳态中枢控制的缺陷可能是某些类型的肥胖相关II型糖尿病的另一个因素。
