当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid-induced insulin resistance in cardiomyocytes.

Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid-induced insulin resistance in cardiomyocytes.

Abstract：

:During lipid oversupply, the heart becomes insulin resistant, as exemplified by defective insulin-stimulated glucose uptake, and will develop diastolic dysfunction. In the healthy heart, not only insulin, but also increased contractile activity stimulates glucose uptake. Upon increased contraction both AMP-activated protein kinase (AMPK) and protein kinase D (PKD) are activated, and mediate the stimulation of glucose uptake into cardiomyocytes. Therefore, each of these kinases is a potential therapeutic target in the diabetic heart because they may serve to bypass defective insulin-stimulated glucose uptake. To test the preventive potential of these kinases against loss of insulin-stimulated glucose uptake, AMPK or PKD were adenovirally overexpressed in primary cultures of insulin resistant cardiomyocytes for assaying substrate uptake, insulin responsiveness and lipid accumulation. To induce insulin resistance and lipid loading, rat primary cardiomyocytes were cultured in the presence of high insulin (100 nM; HI) or high palmitate (palmitate/BSA: 3/1; HP). HI and HP each reduced insulin responsiveness, and increased basal palmitate uptake and lipid storage. Overexpression of each of the kinases prevented loss of insulin-stimulated glucose uptake. Overexpression of AMPK also prevented loss of insulin signaling in HI- and HP-cultured cardiomyocytes, but did not prevent lipid accumulation. In contrast, overexpression of PKD prevented lipid accumulation, but not loss of insulin signaling in HI- and HP-cultured cardiomyocytes. In conclusion, AMPK and PKD prevent loss of insulin-stimulated glucose uptake into cardiomyocytes cultured under insulin resistance-inducing conditions through different mechanisms. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Steinbusch LK,Dirkx E,Hoebers NT,Roelants V,Foretz M,Viollet B,Diamant M,van Eys G,Ouwens DM,Bertrand L,Glatz JF,Luiken JJ

doi

10.1016/j.yjmcc.2012.11.005

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

165-73

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(12)00406-3

journal_volume

pub_type

杂志文章

在线工具

Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid-induced insulin resistance in cardiomyocytes.