Activation of KATP channels suppresses glucose production in humans

被引：89

作者：

Kishore, Preeti ^{[1
]}

Boucai, Laura ^{[1
]}

Zhang, Kehao ^{[1
]}

Li, Weijie ^{[1
]}

Koppaka, Sudha ^{[1
]}

Kehlenbrink, Sylvia ^{[1
]}

Schiwek, Anna ^{[1
]}

Esterson, Yonah B. ^{[1
]}

Mehta, Deeksha ^{[1
]}

Bursheh, Samar ^{[1
]}

Su, Ya ^{[1
]}

Gutierrez-Juarez, Roger ^{[1
]}

Muzumdar, Radhika ^{[1
]}

Schwartz, Gary J. ^{[1
]}

Hawkins, Meredith ^{[1
]}

机构：

[1] Albert Einstein Coll Med, New York, NY USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2011年 / 121卷 / 12期

基金：

美国国家卫生研究院;

关键词：

BRAIN-INSULIN ACTION; LIVER; HOMEOSTASIS; METABOLISM; NEURONS; RATS; DOGS; CNS;

D O I：

10.1172/JCI58035

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：4916 / 4920

页数：5

共 28 条

[1] Influence of ATP-dependent K+-channel opener on K+-cycle and oxygen consumption in rat liver mitochondria [J].