Interrelation between thyroid state and the effect of glucagon on gluconeogenesis in perfused rat livers

The effects of different thyroid states on glucagon/dBcAMP-induced gluconeogenesis from alanine or lactate were investigated in the isolated perfused liver from 24-hr starved rats. Gluconeogenesis from alanine varied with the thyroid state, being increased in hyperthyroidism and decreased in hypothyroidism. Both glucagon and dBcAMP increased glucose production from alanine in euthyroid and even less pronounced in hypothyroid livers, the effect was dose dependent; concomitantly alanine and [14C] alpha-amino-isobutyric acid uptake increased. In hyperthyroid liver, both glucagon and dBcAMP stimulated neither hepatic uptake of alanine and [14C] alpha-amino-isobutyric acid nor gluconeogenesis from alanine. Lactate uptake as well as glucose production from lactate varied with the thyroid state, being increased in the hyper- and decreased in the hypothyroid state. Both glucagon and dBcAMP increased lactate uptake as well as gluconeogenesis from lactate: the effect was even more pronounced in hyperthyroid and reduced in hypothyroid liver. We conclude that the glucogenic effect of glucagon/dBcAMP is reduced in the hypo- and--at unlimited substrate supply--stimulated in the hyperthyroid liver.