Insulin and dexamethasone stimulation of cardiac lipoprotein lipase activity involves the actin-based cytoskeleton.
Lipoprotein lipase (LPL) activity in cultured ventricular cardiomyocytes from adult rat hearts was stimulated by the combination of insulin (100 nM) and dexamethasone (100 nM) during an overnight (16 h) incubation. Wortmannin (100 nM), rapamycin (30 ng/ml) or PD98059 (50 microM) did not prevent this stimulation, suggesting that phosphatidylinositol 3-kinase, p70 S6 kinase and the mitogen-activated protein kinase cascade are not involved in transducing the hormonal signal. In contrast, cytochalasin D (2 microM) completely abolished the stimulatory effect of insulin and dexamethasone on both heparin-releasable LPL and total cellular LPL activities. The potential role of the actin cytoskeleton in the stimulation of LPL activity by insulin and dexamethasone appears to be distal to the initial signalling events since cytochalasin D is still effective in preventing the stimulation when added 2 h after the hormones.
Ewart
H S
HS
University of Calgary, Department of Pharmacology and Therapeutics, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 4N1.
Severson
D L
DL
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D000199:Actins; D004791:Enzyme Inhibitors; D007328:Insulin; D015638:Cytochalasin D; D003907:Dexamethasone; D008071:Lipoprotein Lipase