Regulation of renal and hepatic pyruvate dehydrogenase complex on carbohydrate re-feeding after starvation. Possible mechanisms and a regulatory role for thyroid hormone.
The work investigated the mechanisms for modulation of renal and hepatic pyruvate dehydrogenase complex (PDH) activities after carbohydrate re-feeding of 48 h-starved rats, and identified a regulatory role for tri-iodothyronine. Glucose re-feeding decreased blood concentrations of lipid fuels in both euthyroid and hyperthyroid rats. This treatment was not associated with re-activation of hepatic PDH in either group of rats, or of renal PDH in hyperthyroid rats (where activity was already high), but it increased renal PDH in euthyroid rats. Dichloroacetate (DCA), an activator of PDH kinase, increased renal PDH activities in euthyroid rats, but not hyperthyroid rats, and effects of glucose re-feeding or hyperthyroidism were no longer apparent. These treatments therefore exert their effects on renal PDH through changes in PDH kinase. DCA re-activation of hepatic PDH was more marked in hyperthyroid than in euthyroid rats, suggesting that, under conditions of inhibited kinase activity, PDH phosphatase is more active in livers of hyperthyroid rats. The limited effect of DCA on hepatic PDH in euthyroid rats was potentiated by glucose re-feeding or insulin, but not by inhibition of lipolysis, demonstrating a direct effect of insulin to increase hepatic PDH phosphatase. Glucose re-feeding, inhibition of lipolysis or insulin administration did not increase hepatic PDH in DCA-treated hyperthyroid rats, indicating that effects of hyperthyroidism and of insulin on PDH phosphatase are not additive.
Holness
M J
MJ
Sugden
M C
MC
D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005260:Female; D005502:Food; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D011720:Pyrazoles / Q000494:pharmacology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D004040:Dietary Carbohydrates; D007328:Insulin; D011720:Pyrazoles; D011768:Pyruvate Dehydrogenase Complex; D014284:Triiodothyronine; D003999:Dichloroacetic Acid; D005947:Glucose; C005210:5-methylpyrazole-3-carboxylic acid