Cimetidine blockade of histamine-induced insulin secretion

The effects of an H2-histamine receptor antagonist, cimetidine, on histamine-induced changes in plasma levels of insulin, free fatty acids (FFAs), and glucose was examined in a randomized, double-blind study in six fasted men. The intravenous infusion of histamine at an average rate of 0.13 microgram/kg/min for 20 min caused a rapid rise in plasma insulin levels throughout the infusion period (p < 0.05). Insulin levels rose 23% above baseline after 5 min of infusion and continued to 51% above baseline 10 min after the infusion ended. Cimetidine pretreatment (300 mg intravenously) inhibited histamine-induced insulin secretion by 98% or more at each point during the infusion (p < 0.05), but did not inhibit an effect of histamine to elevate plasma FFA levels. Plasma FFA levels were increased 33% by histamine alone and 41% by histamine when subjects had been pretreated with cimetidine (p < 0.05). Plasma glucose levels were not affected by histamine or cimetidine. These findings demonstrate that histamine is capable of inducing insulin secretion in man at low doses. Blockade of this effect with cimedine suggests that the mechanism of histamine-induced insulin secretion involves the H2-histamine receptor.