Involvement of endogenous epinephrine in histamine-induced hyperinsulinemia and hypoglycemia in rats treated with islet-activating protein

Abstract

Islet-activating protein (IAP), purified from the culture medium of Bordetella pertussis, was injected i.v. into rats at a dose of 5 μg/kg. While the injection of histamine caused hyperglycemia in normal rats, it caused marked hypoglycemia associated with hyperinsulinemia in IAP-treated rats. No hypoglycemia developed after histamine if the IAP-treated rats had been adrenodemedullated or injected with a β-adrenergic antagonist or with anti-insulin serum. Histamine-induced hyperinsulinemia in IAP-treated rats was also abolished by adrenodemedullation or a β-adrenergic antagonist. Ether anesthesia, which provokes the release of epinephrine from the adrenal medullae, mimicked the action of histamine in both normal and IAP-treated rats. Histamine did not influence insulin secretion when it was added directly to the incubation medium islets isolated from IAP-treated rats. It is concluded that epinephrine released from the adrenal medullae in response to histamine challenge enhances insulin secretion via the β-adrebergic receptors, thereby causing severe hypoglycemia in IAP-treated rats.