Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice
Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice
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DOI：
10.1007/s00125-005-1838-8
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发表时间：
2005-08-01
期刊：
影响因子：
8.2
通讯作者：
Corssmit, EPM
中科院分区：
文献类型：
--
作者：
Heijboer, AC;van den Hoek, AM;Corssmit, EPM
目的/假设：本研究旨在评价中枢应用阿糖皮质素-3/4受体激动剂黑色素II(MTII)对肝脏和全身胰岛素敏感性的影响，该效应与食物摄入量和体重无关。方法：雄性C57B1/6小鼠左侧脑室注射MTII 225 ng，持续24 h。这些动物无法获得食物。对照组注射三针蒸馏水。采用高胰岛素正血糖钳夹结合[H-3]葡萄糖输注的方法测定全身和肝脏的胰岛素敏感性。检测骨骼肌组织中GLUT4mRNA的表达。结果：MTII组和安慰剂组小鼠在基础状态和高胰岛素血症条件下的血糖和胰岛素浓度相似。MTII处理组小鼠的内源性葡萄糖产生(EGP)和基础状态下的葡萄糖处置显著高于对照组(71+/-22vs43+/-12mU·moL)。分钟(-1)。Kg(-1)，p<；0.01)。在高胰岛素血症期间，MTII治疗组小鼠的葡萄糖处置显著高于对照组(151+/-20vs108+/-20mU·mo.分钟(-1)。Kg(-1)，p<；0.01)。而胰岛素对EGP的抑制作用不受MTII的影响(EGP相对下降：45+/-27vs50+/-20%)。MTII组小鼠骨骼肌GLUT4mRNA表达显著增加(307+/-94vs100+/-56%，p<；0.01)。结论/解释：脑室注射MTII可显著增加C57B1/6小鼠胰岛素介导的葡萄糖处置，但不影响胰岛素抑制EGP的能力。这些数据表明，中枢刺激黑素皮质素-3/4受体以一种组织特异性的方式调节胰岛素敏感性，与众所周知的对进食和体重的影响无关。
Aims/hypothesis: The present study was conducted to evaluate the effects of central administration of melanotan II ( MTII), amelanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Methods: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left lateral ventricle of male C57B1/6 mice. The animals had no access to food. The control group received three injections of distilled water. Whole-body and hepatic insulin sensitivity were measured by hyperinsulinaemic euglycaemic clamp in combination with [H-3] glucose infusion. Glut4 mRNA expression was measured in skeletal muscle. Results: Plasma glucose and insulin concentrations under basal and hyperinsulinaemic conditions were similar in MTII- and placebo- treated mice. Endogenous glucose production ( EGP) and glucose disposal in the basal state were significantly higher in MTII- treated mice than in the control group ( 71 +/- 22 vs 43 +/- 12 mu mol . min(-1) . kg(-1), p < 0.01). During hyperinsulinaemia, glucose disposal was significantly higher in MTII- treated mice (151 +/- 20 vs 108 +/- 20 mu mol . min(-1) . kg(-1), p < 0.01). In contrast, the inhibitory effect of insulin on EGP was not affected by MTII ( relative decrease in EGP: 45 +/- 27 vs 50 +/- 20%). Glut4 mRNA expression in skeletal muscle was significantly increased in MTII-treated mice (307 +/- 94 vs 100 +/- 56%, p < 0.01). Conclusions/ interpretation: Intracerebroventricular administration of MTII acutely increases insulin-mediated glucose disposal but does not affect the capacity of insulin to suppress EGP in C57B1/ 6 mice. These data indicate that central stimulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue- specific manner, independent of its well-known impact on feeding and body weight.