Starvation-induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo.
The role of thyroid hormones in the metabolic adaptation to starvation was investigated in vivo. Glucose production, measured by tracer technique, was enhanced in hyperthyroid (185%) and reduced in hypothyroid (39%) 48-hour starved rats (euthyroid control = 100%). Urinary nitrogen excretion was increased in hyperthyroidism (132%) and decreased in hypothyroidism (70%). Compared with euthyroid controls (=100%) significant alterations for the following regulatory parameters of hepatic gluconeogenesis were observed: 1) tissue cAMP (124%/91%) and protein kinase activation (132%/90%), with a corresponding crossover between pyruvate and P-enolpyruvate (-/+/+/-); 2) pyruvate carboxylase (165%/60%), P-enolpyruvate carboxykinase (140%/82%) and fructose-1.6-bis-P-phosphatase activity (99%/61%), and 3) tissue content of the glucogenic amino acids: alanine (187%/66%) and glutamate (187%/88%), aspartate (179%/68%) and glutamate (137%/75%), as well as of oxaloacetate (254%/66%) and malate (164%/104%). The observed alterations in hepatic oligomycine-sensitive oxygen consumption in hyper- (161%) and hypothyroidism (51%) were related to the measured concentration of the intermediates of the citric acid cycle, the energy state and the mitochondrial redox state. In summary, the different rates of hepatic glucose production in hyper- and hypothyroid starved rats observed in vivo can be ascribed to 1) cAMP content, 2) gluconeogenic key enzyme activities, 3) glucogenic precursor supply and 4) cofactor (ATP) availability.
D000818:Animals; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D005943:Gluconeogenesis; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000652:urine; D010084:Oxidation-Reduction; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D013217:Starvation / Q000378:metabolism*
D002951:Citrates; D011773:Pyruvates; D019343:Citric Acid; D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D009584:Nitrogen