Interactive effects of insulin and triiodothyronine on pyruvate dehydrogenase kinase activity in cardiac myocytes.
Hyperthyroidism [produced by the administration of 3,5,3'-triiodothyronine (T3) for 3 days to adult rats] increased PDH kinase activities of freshly isolated cardiomyocytes by 1.6-fold. The effects of hyperthyroidism and 48 h-starvation to increase PDH kinase activities were additive. Culture of cardiomyocytes prepared from fed, euthyroid rats for 25 h with T3 (100 nM) increased PDH kinase activities to values comparable in magnitude to those observed in response to experimental hyperthyroidism in vivo. PDH kinase activities in cardiomyocytes from fed, euthyroid rats after culture with n-octanoate (1 mM) or dibutyryl cyclic AMP (DBcAMP)(50 microM) exceeded those of freshly isolated myocytes. DBcAMP and T3 were without further effect in the presence of n-octanoate. The inclusion of insulin (100 microU/ml) alone in the culture medium did not affect PDH kinase activity, but insulin suppressed the effects of T3, DBcAMP and n-octanoate to increase cardiomyocyte PDH kinase activity in culture. PDH kinase activities in cardiomyocytes isolated from starved rats declined after 25 h of culture. This decline was prevented by the inclusion of T3, but not of DBcAMP, in the culture medium. Insulin (100 microU/ml) suppressed the effects of T3 to oppose the loss of cardiomyocyte PDH kinase activity experienced during culture. The results demonstrate that hyperthyroidism leads to a stable increase in the activity of cardiomyocyte PDH kinase, a response that is mimicked by T3 in vitro. Insulin opposes the effects of T3 (and of fatty acids and cyclic AMP) to increase PDH kinase activity in cultured cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Orfali
K A
KA
Department of Biochemistry, Queen Mary & Westfield College (University of London), UK.
Fryer
L G
LG
Holness
M J
MJ
Sugden
M C
MC
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology*
D007328:Insulin; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014284:Triiodothyronine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases