Beta adrenergic receptor dysfunction in hypoxic inhibition of insulin release

Insulin secretory responses were measured in air-breathing puppies given epinephrine, and compared with insulin responses during acute hypoxia. In puppies with oxygen deficiency, insulin levels declined, whereas during epinephrine infusion, they remained stable or increased slightly. When glucose was given during phentolamine administration, insulin levels rose more in the epinephrine-treated animals than in the hypoxic animals, despite similar blood glucose levels. Theophylline-induced insulin release was increased by epinephrine, but inhibited by hypoxia. When the beta adrenergic blocking agent, propranolol, was given with the epinephrine, the insulin response to theophylline was markedly reduced and similar to that observed during hypoxia. Control studies with propranolol showed no effect of this agent on glucose-induced insulin release. Isoproterenol infusion caused elevated insulin levels during air ventilation but this response was suppressed by hypoxia. From these data, we have concluded that the difference between hypoxia and epinephrine can be explained by a reduced ability of catecholamines to stimulate the beta adrenergic receptor during hypoxia. We hypothesize that this effect leads to an unmodulated alpha adrenergic inhibition of insulin release.