Metabolic and hormone-related responses to caffeine in rats

The time course of effects of caffeine on plasma glucose and non-esterified fatty acids (NEFA) were measured and related to various hormonal responses associated with substrate mobilization and utilization. Participation of the sympatho-adrenal system (SAS) in the metabolic and hormonal actions of caffeine was also investigated by the use of ganglionic blockade. Following 50 mg kg-1 i.p. injections of caffeine in rats, plasma glucose increased 25% and NEFA 40%, and these actions were parallelled by an elevation of plasma insulin, ACTH and corticosterone, without changes in glucagon. It is suggested that the insulin response is related to the plasma glucose increase and possibly also to an action of cAMP. When caffeine was injected in rats previously treated with the ganglionic blocker, hexamethonium, none of the responses mentioned above were modified. These results show that the glucose and NEFA responses are independent of glucagon secretion and are due not only to SAS activation but also to other mechanisms such as the increased ACTH and corticosterone secretion. It is also suggested that the mobilization of substrates by caffeine is mediated, through these various mechanisms, by the activation of cAMP and by phosphodiesterase inhibition.