Effects of glucagon and 3,5,3'-triiodo-L-thyronine on oxidative phosphorylation of thyroidectomized rat liver mitochondria

In normal or thyroidectomized rat liver mitochondria, glucagon produced fast but transient stimulation of respiration rates in state 3 and state 4 whatever the substrates. Stimulation reached its maximum 20 to 30 minutes after glucagon injection. However, the effects of glucagon are less marked after removal of the thyroid gland, since the increases observed in the oxygen consumption and basal metabolic rates were only half those shown in normal rats. The activating effects of triiodothyronine and glucagon on the ADP phosphorylation rates were found to be additive. Pretreatment with cycloheximide blocked the activation induced by glucagon but not that induced by triiodothyronine. Both hormones therefore stimulate oxidative phosphorylation but by different mechanisms. Thyroidectomy did not alter the early rise in glycaemia observed in response to glucagon. It may therefore be assumed that the hypothyroid rat's sensitivity to glucagon is not directly connected with the change in cAMP metabolism.