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.