Isoproterenol- and epinephrine-induced changes in blood glucose and tissue glycogen levels in normal and diabetic rats: the influence of alteration in endogenous insulin levels and state of nourishment.

The hyperglycemic activities of catecholamines vary drastically from one species to another. Within certain species, the activity of catecholamines is largely dependent upon the state of nourishment. In the rat, isoproterenol (ISO) produces significant hyperglycemia only in the fasted state whereas epinephrine (EPI) produces hyperglycemia in both the fed and the fasted states. In this study, measurement of plasma insulin and glucose levels in response to ISO and EPI showed that ISO produces dose-related increases in the insulin/glucose ratio and that the ratio is influenced greatly by the state of nourishment. On the other hand, EPI, an inhibitor of insulin release, reduced the insulin/glucose ratio. When a deficiency of insulin release was produced by alloxan treatment, the hyperglycemic activity of ISO was increased markedly whereas the activity of EPI did not change. Pretreatment of fed normal rats with ISO suppressed markedly the expected hyperglycemic response to a subsequent challenge with EPI. In contrast, injection of ISO prior to an EPI challenge in diabetic rats produced a hyperglycemic effect greater than that produced by either agent alone. These results suggest that insulin release by ISO regulates the hyperglycemic activity of this catecholamine in the rat and perhaps in several other species as well. Moreover, much of the species differences in the hyperglycemic activity of catecholamines can be attributed to their ability to stimulate hepatic glucose production on the one hand and to stimulate or inhibit insulin release on the other.