Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation

被引：111

作者：

Jeoung, Nam Ho

Wu, Pengfei

Joshi, Mandar A.

Jaskiewicz, Jerzy

Bock, Cheryl B.

DePaoli-Roach, Anna A.

Harris, Robert A.

机构：

[1] Indiana Univ, Sch Med, Biotechnol Res & Training Ctr, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[2] Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA

来源：

BIOCHEMICAL JOURNAL | 2006年 / 397卷 / 417-425期

关键词：

branched chain amino acid; fatty acid oxidation; glucose homoeostasis; pyruvate dehydrogenase complex; pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency; starvation;

D O I：

10.1042/BJ20060125

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation during starvation to conserve substrates for gluconeogenesis. The role of PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this mechanism was investigated with PDHK4(-/-) mice (homozygous PDHK4 knockout mice). Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type mice. The activity state of PDC (percentage dephosphorylated and active) is greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver of starved PDHK4(-/-) mice. Intermediates of the gluconeogenic pathway are lower in concentration in the liver of starved PDHK4(-/-) mice, consistent with a lower rate of gluconeogenesis due to a substrate supply limitation. The concentration of gluconeogenic substrates is lower in the blood of starved PDHK4(-/-) mice, consistent with reduced formation in peripheral tissues. Isolated diaphragms from starved PDHK4(-/-) mice accumulate

引用

页码：417 / 425

页数：9

共 41 条

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