Activation of KATP channels suppresses glucose production in humans
Activation of KATP channels suppresses glucose production in humans
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DOI：
10.1172/jci58035
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发表时间：
2011-12-01
影响因子：
15.9
通讯作者：
Hawkins, Meredith
中科院分区：
文献类型：
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作者：
Kishore, Preeti;Boucai, Laura;Hawkins, Meredith
内源性葡萄糖生成增加(EGP)是2型糖尿病的一个标志。虽然有证据表明啮齿类动物通过激活下丘脑三磷酸腺苷敏感钾(K-ATP)通道来对EGP进行中枢调节，但这些中枢通路是否对人类EGP的调节起作用仍有待确定。在这里，我们提出了人类中枢神经系统EGP调节的证据，这与补充的啮齿动物研究是一致的。在固定的激素条件下，口服K-ATP通道激活剂二氮嗪可显著降低非糖尿病人和SpragueDawley大鼠的EGP。在大鼠中，相同剂量的口服二氮卓在脑脊液中达到了可察觉的浓度，口服二氮卓的作用被静脉注射取消。使用K-ATP通道阻滞剂格列本脲。这些结果提示，下丘脑K-ATP通道的激活可能是人类EGP的重要调节途径，该途径可能是治疗2型糖尿病高血糖的靶点。
Increased endogenous glucose production (EGP) is a hallmark of type 2 diabetes mellitus. While there is evidence for central regulation of EGP by activation of hypothalamic ATP-sensitive potassium (K-ATP) channels in rodents, whether these central pathways contribute to regulation of EGP in humans remains to be determined. Here we present evidence for central nervous system regulation of EGP in humans that is consistent with complementary rodent studies. Oral administration of the K-ATP channel activator diazoxide under fixed hormonal conditions substantially decreased EGP in nondiabetic humans and Sprague Dawley rats. In rats, comparable doses of oral diazoxide attained appreciable concentrations in the cerebrospinal fluid, and the effects of oral diazoxide were abolished by i.c.v. administration of the K-ATP channel blocker glibenclamide. These results suggest that activation of hypothalamic K-ATP, channels may be an important regulator of EGP in humans and that this pathway could be a target for treatment of hyperglycemia in type 2 diabetes mellitus.