Mizuno A, Murakami T, Doi T, Shima K
Department of Laboratory Medicine, School of Medicine, The University of Tokushima, Kuramotocho 3-chome, 770-8503, Tokushima, Japan.
Regul Pept. 2001 May 5;99(1):41-4. doi: 10.1016/s0167-0115(01)00215-4.
Leptin has been proposed to be a sensor of energy storage in adipose tissues, and is capable of mediating a feedback signal to the hypothalamus, which is involved in the regulation of energy homeostasis and body weight. In order to investigate the issue of whether resistance to the activity of leptin on insulin sensitivity is observed in young Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 8 weeks of age, leptin (50 nmol/kg/h) was administered intravenously for 16 h to OLETF and Long-Evans Tokushima Otsuka (LETO) (lean controls) rats, followed by a measurement of insulin-stimulated glucose uptake in hindlimb muscles during hyperinsulinemic euglycemic clamp technique. In the case of LETO rats, the administration of leptin significantly decreased plasma insulin levels prior to the clamp test, but did not change plasma glucose levels. Furthermore, leptin led to an increase in insulin-stimulated glucose uptake in hindlimb muscles. However, in the case of OLETF rats, leptin administration changed neither plasma insulin levels nor insulin-stimulated glucose uptake. These data demonstrate that OLETF rats at 8 weeks of age have already become resistant to high concentration of peripheral leptin.
瘦素被认为是脂肪组织中能量储存的传感器，能够介导向参与能量稳态和体重调节的下丘脑传递反馈信号。为了研究8周龄的大冢朗-伊云斯-德岛肥胖（OLETF）大鼠是否存在对瘦素作用于胰岛素敏感性的抵抗，将瘦素（50 nmol/kg/h）静脉注射给OLETF和朗-伊云斯-德岛大冢（LETO）（瘦对照）大鼠16小时，然后在高胰岛素正常血糖钳夹技术期间测量后肢肌肉中胰岛素刺激的葡萄糖摄取。对于LETO大鼠，在钳夹试验前给予瘦素显著降低了血浆胰岛素水平，但未改变血浆葡萄糖水平。此外，瘦素导致后肢肌肉中胰岛素刺激的葡萄糖摄取增加。然而，对于OLETF大鼠，给予瘦素既未改变血浆胰岛素水平，也未改变胰岛素刺激的葡萄糖摄取。这些数据表明，8周龄的OLETF大鼠已经对外周高浓度瘦素产生了抵抗。
