ABSTRACT
The resistance to the effects of glucagon was studied in isolated hepatocytes prepared from male rats treated with 6N-propyl-2-thiouracil (PTU). Incorporation of [14C]oleate into ketone bodies in response to various concentrations of glucagon (10(-5) to 10(-10) M) was reduced in hepatocytes from hypothyroid rats compared with the euthyroid group. The reduced sensitivity to the effects of glucagon on ketogenesis after treatment with PTU was associated with a reduced ability of those hepatocytes to maintain cyclic adenosine-3',5'-monophosphate (cAMP) at levels required to stimulate ketogenesis. The concentration of cAMP in response to glucagon (10(-5) to 10(-10) M) was diminished in hepatocytes from hypothyroid rats, compared with those from euthyroid animals.