The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus.
The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus.
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DOI：
10.1038/ijo.2013.53
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发表时间：
2014-01
期刊：
影响因子：
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通讯作者：
Vaisse C
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文献类型：
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作者：
Aslan IR;Ranadive SA;Valle I;Kollipara S;Noble JA;Vaisse C
中枢黑皮质素系统对于人类长期能量稳态的调节是必不可少的。啮齿动物实验表明，该系统也影响葡萄糖代谢，特别是通过调节外周胰岛素敏感性独立于其对肥胖的影响。在中枢黑皮质素系统中具有完全遗传缺陷的罕见患者可以深入了解该系统在人类葡萄糖稳态中的作用。在这里，我们描述了第八个人完全POMC缺乏症和第一个巧合伴随I型糖尿病，这提供了一个独特的机会，以确定黑皮质素在人体葡萄糖稳态的作用。对这例单独ACTH缺乏的严重肥胖患者的POMC基因进行直接测序，发现了一个纯合的5′ UTR突变− 11 C>A，我们发现该突变破坏了正常的POMC蛋白合成，体外评估结果显示。患者的胰岛素需求与其年龄和青春期发育的预期一致。这个独特的病人表明，在人类中，中枢黑皮质素系统似乎不影响外周胰岛素敏感性，独立于其对肥胖的影响。
The central melanocortin system is essential for the regulation of long-term energy homeostasis in humans. Rodent experiments suggest that this system also affects glucose metabolism, in particular by modulating peripheral insulin sensitivity independently of its effect on adiposity. Rare patients with complete genetic defects in the central melanocortin system can provide insight into the role of this system in glucose homeostasis in humans. We here describe the eighth individual with complete POMC deficiency and the first with coincidental concomitant Type I Diabetes, which provides a unique opportunity to determine the role of melanocortins in glucose homeostasis in human. Direct sequencing of the POMC gene in this severely obese patient with isolated ACTH deficiency identified a homozygous 5′ UTR mutation −11C>A which we find to abolish normal POMC protein synthesis, as assessed in vitro. The patient’s insulin requirements were as expected for his age and pubertal developmental. This unique patient suggests that in humans, the central melanocortin system does not seem to affect peripheral insulin sensitivity, independently of its effect on adiposity.