FURTHER STUDIES ON THE METABOLIC EFFECTS OF DIAZOXIDE

¹ Department of Physiology and Biochemistry, Schering Corporation, Bloomfield, New Jersey

It has been demonstrated that the attenuated diazoxide hyperglycemia observed in hypophysectomized rats can be fully restored by forced feedings, indicating that the attenuation is not due to a deficiency of some hypophyseal principle, but rather to inanition. Further, the reduction in the ability of diazoxide to elicit hyperglycemia in adrenalectomized mice has been shown to be due to lack of corticoids, since adrenalectomized mice, treated with cortisol, respond normally to diazoxide.

Our earlier speculation that catecholamines are involved in diazoxide hyperglycemia received further support. Bretylium and chlorisondamine attenuate diazoxide hyperglycemia. Epinephrine hyperglycemia was potentiated when it was administered with diazoxide.

Diazoxide elicits a mobilization of free fatty acids (FFA) in dogs and rats; increases in plasma FFA and glucose in dogs are inhibited by N-isopropylmethoxamine, an agent which blocks the hyperglycemia and increased FFA due to catecholamines.

Evidence to date strongly indicates a role of the catecholamines in diazoxide-induced hyperglycemia and increased FFA.

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