The mode of action of insulin potentiation by mebanazine
- 12 April 1970
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 22 (4), 291-297
- https://doi.org/10.1111/j.2042-7158.1970.tb08521.x
Abstract
Chronic oral treatment of rats with mebanazine potentiated the hypoglycaemic response to insulin both in intensity and duration. A similar potentiation of intensity but not of duration was observed in pair-fed animals. In consequence, mebanazine-treated rats subjected to a 21 h fast before insulin died in hypoglycaemic coma whereas control and pair-fed animals did not. Intravenous glucose brought about a rapid return to consciousness in moribund mebanazine-treated rats in insulin coma but hyperglycaemic catecholamines did not. The observed hypoglycaemic unresponsiveness was not solely due to depletion of liver glycogen since both control and treated rats had undetectable levels of glycogen after fasting, yet only the treated animals died. Tissue levels of noradrenaline were raised by mebanazine treatment in brain, heart and liver but these enlarged stores were readily depleted by reserpine. A similar potentiation of hypoglycaemia was observed following chronic treatment of intact rats with tranylcypromine and of adreno-demedullated rats with guanethidine and bethanidine. No potentiation was observed with reserpine or α-methyldopa in either type of animal. Blood glucose was significantly raised by adrenaline and α-methylnoradrenaline, but not by octopamine. The observations support the hypothesis that hypoglycaemic unresponsiveness following chronic inhibition of monoamine oxidase is due to a replacement of noradrenaline in adrenergic neurons by octopamine. This substance is an ineffective hyperglycaemic agent and its physiological release in response to hypoglycaemia does not bring about a return to normoglycaemia.Keywords
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