The expression and function of histamine H3 receptors in pancreatic beta cells

Tadaho Nakamura, T. Yoshikawa, N. Noguchi, A. Sugawara, Atsuko Kasajima, H. Sasano, K. Yanai

研究成果: Article査読

17 被引用数 (Scopus)

抄録

Background and Purpose Histamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin. Experimental Approach The expression of histamine receptors in pancreatic beta cells was examined by RT-PCR, Western blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H3 receptors in glucose-induced insulin secretion (GIIS) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H3 receptors in MIN6 cell proliferation were examined using pharmacological assay and Western blotting. Key Results Histamine H 3 receptors were expressed in pancreatic beta cells. A selective H3 receptor agonist, imetit, and a selective inverse H3 receptor agonist, JNJ-5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ-5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl, indicating that GIIS signalling was affected by H3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element-binding protein (CREB), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H 3 receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation. Conclusions and Implications Histamine H3 receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation.

本文言語English
ページ(範囲)171-185
ページ数15
ジャーナルBritish Journal of Pharmacology
171
1
DOI
出版ステータスPublished - 2014 1

ASJC Scopus subject areas

  • 薬理学

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