Neurotensin Hyperglycemia: Evidence for Histamine Mediation and the Assessment of a Possible Physiologic Role

Abstract

The hyperglycemic and hyperglucagonemic effects of systemically administered neurotensin in rats were investigated to explore the possibility that they are mediated by histamine and to determine whether neurotensin might have a role in the mediation of the responses to central nervous system glucopenia. The hyperglycemic response to neurotensin was partially blocked by the histamine H-l receptor blockers, diphenhydramine and promethazine, and by the H-2 receptor blocker, cimetidine. The hyperglucagonemic response was completely blocked by diphenhydramine and promethazine and only partially blocked by cimetidine. The effects of histamine on glucose, glucagon, and insulin secretion were similar to those of neurotensin, and the inhibitory effects of both H-l and H-2 blockers were comparable. The stimulatory effect of histamine on insulin secretion observed after adrenal autotransplantation was also similar to that previously reported for neurotensin. Neither antineurotensin serum nor diphenhydramine, however, was effective in blocking the hyperglycemic and hyperglucagonemic responses to the central administration of 2-deoxyglucose. The results are consistent with a histamine mediation of the effects of exogenously administered neurotensin but do not support a proposed role for neurotensin or histamine in the mediation of the hyperglycemic and hyperglucagonemic responses to central glucopenia.