Effects of histamine, of histidine and of anti-histaminic agents on the release of glucagon and insulin from the rat pancreas.

We have studied the effect of histamine (HA) and histidine (HIS) on the release of immunoreactive glucagon (IRG) and insulin (IRI) by isolated rat islets and pieces of pancreas. In isolated islets, HA and HIS stimulated IRG release at a glucose concentration of 3.0 mg/ml and IRI release at a glucose concentration of 0.5 mg/ml. In pieces of pancreas incubated in the presence of glucose (3.0 mg/ml), HA at a 2mM concentration stimulated IRG release and had no effect on the release of IRI; however, when the concentration of HA was doubled (4 mM), an inhibition of IRI release could also be demonstrated. HIS was ineffective. Perphenazine and dexchlorpheniramine, two anti-histaminic agents, inhibited IRG and stimulated IRI release. These results indicate that histamine, whether endogenous or exogenous, directly stimulated IRG and inhibits IRI release and suggest that some of the in vivo effects of histamine, such as hyperglycemia and lipid mobilization, may be mediated, at least in part, by these endocrinologic effects.