Untersuchungen zur Regulation des Glucosetransportes durch cGMP in isolierten Herzmuskelzellen adulter Ratten

Recent evidence points to a potential role of cyclic GMP (cGMP) in the control of cardiac glucose utilization. The present work examines whether the glucose transport system of cardiac myocyte is a site of this cGMP-dependent regulation. Treatment of isolated rat cardiomyocytes (for 10 min) with the membrane-permeant cGMP analogue 8-(4-chlorophenylthio)-cGMP (8-p-CPT-cGMP, 200 µM) caused a decrease in glucose transport in non-stimulated (basal) myocytes, as well as in cells stimulated with insulin or with the mitochondrial inhibitor oligomycin B by up to 40%. An inhibitory effect was also observed with another cGMP analogue (8-bromo-cGMP), and in cells stimulated by hydrogen peroxide or anoxia. In contrast, 8-p-CPT-cAMP (200 µM), or the b-adrenergic agonist isoprenaline (which increases cAMP levels) did not depress glucose transport, and even potentiated the effect of insulin. Blockade of endogenous cGMP formation with the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 µM) significantly increased basal and insulin-dependent glucose transport (by 25%), whereas addition of the guanylate cyclase activator 3-(5'-hydroxymethyl-2'furyl)-1-benzylindazol (YC-1, 30 µM) produced a depression of glucose transport (by 20%). In contrast, nitric oxide (NO), another guanylate cyclase activator, had no effect on basal and Insulin-stimulated transport, perhaps due to cGMP-independent effects of NO. Confocal laser scanning microscopic studies revealed that cGMP partially prevents the insulin-induced redistribution of the glucose transporter GLUT4 from intracellular stores to the cell surface. These observations suggest that the glucose transport system of cardiomyocytes represents a metabolic target of inhibition by cGMP, and that this regulation occurs at the level of the trafficking of glucose transporters.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2003

Author dc:creator

• Bergemann, Christian Alexander

Contributors dc:contributor

• Fischer, Yvan

• info:eu-repo/classification/ddc/610
• Medizin
• glucose transport
• cardiomyocytes
• cyclic GMP
• nitric oxide
• GLUT4

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-120724%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:58898