Different effects of histaminergic H1 and H2 antagonists on basal and stimulated insulin and glucagon release in humans

We have evaluated in normal subjects the effect of H₁ antagonists meclastine, dexchlorpheniramine and promethazine) and of the H₂ antagonist cimetide on basal and stimulated IRI and IRG release in 78 healthy subjects. Both cimetidine and H₁ antagonists, acutely administered, reduce fasting IRI levels, placebo being ineffective. Results obtained with single H₁ antagonists are pooled, being generally superimposable. IRG release is unaffected by any treatment. IRI response to arginine is enhanced by H₁ antagonists, while cimetidine is ineffective. Cimetidine enhances the A-cell IRG response to arginine and reduces its response to hypoglycemia. A-cell IRG and total IRG response to arginine or to hypoglycemia are not affected by H₁ antagonists or by placebo. The IRI response to i.v. glucose and the blood-glucose pattern after arginine, i.v. glucose or i.v. insulin, are not affected by cimetidine or by H₁ antagonists.