Histaminergic regulation of pancreatic beta-cell replication and insulin secretion.
Evidence suggest that histamine is required for the diabetogenic agent streptozotocin to exert its toxicity on islet beta-cells. The effects of histamine and L-histidine on the replication and long-term insulin secretion by pancreatic beta-cells were investigated. L-histidine dose-dependently increased insulin secretion and suppressed DNA synthesis without affecting the islet insulin content. Histamine suppressed beta-cell replication but failed to affect the islet content or secretion of insulin. Depletion of islet histamine contents by the specific and irreversible inhibitor of L-histidine decarboxylase, alpha-fluoromethyl-[S] histidine increased islet insulin content but failed to influence the rate of insulin secretion. The present results suggest that exogenously added L-histidine, but not histamine, stimulates insulin secretion 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 specific cell surface receptors.
Sjöholm
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Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004261:DNA Replication; D005260:Female; D006632:Histamine / Q000502:physiology*; D006639:Histidine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D006639:Histidine; D006632:Histamine