Mechanism of resistance to the effects of glucagon on cAMP accumulation and ketogenesis in hyperthyroid rats

ABSTRACT

The mechanism of resistance in hypothyroidism to the effects of glucagon was examined utilizing isolated hepatocytes prepared from male rats made hypothyroid with propyithiouracil [PTU]. The increased activity of the low Km phosphodiesterase in hepatocytes from hypothyroid animals may be responsible for the decline in cAMP concentration, since the addition of methylisobutylxanthine [MIX] to the incubation medium restored the effects of glucagon on cAMP accumulation and ketogenesis in hepatocytes from hypothyroid animals to the same levels as those in the euthyroid control group. The sensitivity to glucagon in both groups was increased. The response to 8-Bromo-cAMP was biphasic, At 10[9] M 8-Bromo-cAMP ketogenesis was significantly lower in hepatocytes from hypothyroid rats than euthyroid. The maximal response to 8-Bromo-cAMP was, however, similar in hepatocytes from either euthyroid or hypothyroid animals