HISTAMINERGIC REGULATION OF PANCREATIC BETA-CELL REPLICATION AND INSULIN-SECRETION

Evidence suggests that histamine is required for the diabetogenic agen t streptozotocin to exert its toxicity on islet beta-cells. The effect s of histamine and L-histidine on the replication and long-term insuli n secretion by pancreatic beta-cells were investigated. L-histidine do se-dependently increased insulin secretion and suppressed DNA synthesi s without affecting the islet insulin content. Histamine suppressed be ta-cell replication but failed to affect the islet content or secretio n of insulin. Depletion of islet histamine contents by the specific an d irreversible inhibitor of L-histidine decarboxylase, alpha-fluoromet hyl-[S] histidine increased islet insulin content but failed to influe nce the rate of insulin secretion. The present results suggest that ex ogenously added L-histidine, but not histamine, stimulates insulin sec retion whereas both substances suppress beta-cell growth. Endogenously formed histamine may have different roles in beta-cell function than exogenously delivered histamine, the latter Likely acting through spec ific cell surface receptors. (C) 1995 Academic Press, Inc.