Studies on the extra-hepatic effects of glucagon in the eviscerated rat

The in vivo effects of glucagon on the metabolism of extra-hepatic tissues have been investigated in eviscerated, functionally hepatectomized rats with intact kidneys. In these animals, even pharmacological amounts of exogenous glucagon did not significantly alter plasma glucose, FFA, or amino acids, compared with saline treatment. The possible secondary release of adrenal catecholamines following such doses of glucagon appeared to be similarly ineffective in increasing the peripheral tissue mobilization of substrates. It was only when the eviscerated animals were pretreated with insulin that the subsequent administration of glucagon or epinephrine elicited significant elevations in plasma FFA. The concomitant evisceration and adrenalectomy did not produce results which were significantly different from evisceration alone. Both kinds of animals required insulin pretreatment before a lipolytic response to glucagon or epinephrine could be demonstrated. This suggests that severe insulin insufficiency itself elicits almost maximum catabolism in these animals and that the further addition of other catabolic hormones such as glucagon or epinephrine cannot increase these catabolic effects, as manifest in plasma concentrations of FFA. These data show an extra-hepatic lipolytic effect of glucagon in vivo, but do not illuminate the significance of this effect in the intact animal.