Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice
Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice
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DOI：
10.1038/sj.ijo.0800899
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发表时间：
1999-06-01
影响因子：
4.9
通讯作者：
Havel, PJ
中科院分区：
文献类型：
--
作者：
Ahrén, B;Havel, PJ
目的：近年来大量研究表明瘦素对糖代谢和胰腺激素分泌有影响。因此，研究了瘦素施用对进食和禁食小鼠中循环葡萄糖、胰岛素和胰高血糖素的影响。交感神经系统的潜在贡献瘦素的影响也examined.DESIGN：重组人或鼠瘦素腹腔内（300 μ g/小鼠每12小时超过24小时）喂养或禁食，正常或化学交感神经切除NMRI小鼠。在基线和24 h后采集血样。MEASUREMENTS：血浆葡萄糖，胰岛素和胰高血糖素浓度。结果：在进食状态（n = 24），瘦素给药不影响24 h后的葡萄糖，胰岛素或胰高血糖素浓度。禁食（n = 24）使体重降低2.2 +/- 0.4 g，血糖降低3.7 +/- 0.4 mmol/l，血浆胰岛素降低138 +/- 35 pmol/l，血浆胰高血糖素降低32 +/- 7 pg/ml。在禁食小鼠中，相对于注射生理盐水的对照动物，人瘦素（n = 24）使血浆葡萄糖增加1.5 +/- 0.2 mmol/l（P = 0.041），血浆胰岛素增加95+/-22 pmol/l（P = 0.018），血浆胰高血糖素增加16 +/- 3 pg/ml（P = 0.025）。在禁食小鼠（n=12）中，鼠瘦素对循环葡萄糖（+ 1.0 +/- 0.2 mmol/l，P = 0.046）、胰岛素（+58 +/- 17 pmol/l，P = 0.038）和胰高血糖素（+ 24 +/- 9 pg/ml，P = 0.018）具有与人瘦素相似的刺激作用，而在进食小鼠（n = 12）中没有显著作用。人瘦素没有影响循环葡萄糖，胰岛素或胰高血糖素在禁食小鼠化学交感神经切除术后6-羟基多巴胺（40 mg/kg静脉注射48 h前禁食; n = 12）。结论：瘦素增加循环葡萄糖，胰岛素和胰高血糖素在24小时禁食小鼠的机制，需要完整的交感神经。
OBJECTIVE: A number of recent studies suggest that leptin has effects on glucose metabolism and pancreatic hormone secretion. Therefore, the effect of leptin administration on circulating glucose, insulin and glucagon in fed and fasted mice was investigated. The potential contribution of the sympathetic nervous system to the effects of leptin was also examined.DESIGN: Recombinant human or murine leptin was administered intraperitoneally (300 mu g/mouse per 12 h over 24 h) to fed or fasted, normal or chemically sympathectomized NMRI mice. Blood samples were collected at baseline and after 24 h.MEASUREMENTS: Plasma concentrations of glucose, insulin and glucagon.RESULTS: In the fed state (n = 24), leptin administration did not affect glucose, insulin or glucagon concentrations after 24 h. Easting (n = 24) reduced body weight by 2.2 +/- 0.4 g, plasma glucose by 3.7 +/- 0.4 mmol/l, plasma insulin by 138 +/- 35 pmol/l, and plasma glucagon by 32 +/- 7 pg/ml. In fasted mice, human leptin (n = 24) increased plasma glucose by 1.5 +/- 0.2 mmol/l (P = 0.041), plasma insulin by 95+/-22 pmol/l (P = 0.018), and plasma glucagon by 16 +/- 3 pg/ml (P = 0.025), relative to saline-injected control animals. Murine leptin exerted similar stimulating effects on circulating glucose (+ 1.0 +/- 0.2 mmol/l, P = 0.046), insulin (+58 +/- 17 pmol/l, P = 0.038) and glucagon (+ 24 +/- 9 pg/ml, P = 0.018) as human leptin in fasted mice (n = 12) with no significant effect in fed mice (n=12). Human leptin did not affect circulating glucose, insulin or glucagon in fasted mice after chemical sympathectomy with 6-hydroxydopamine (40 mg/kg iv 48 h prior to fasting; n = 12).CONCLUSION: Leptin increases circulating glucose, insulin and glucagon in 24 h fasted mice by a mechanism requiring intact sympathetic nerves.