Effects of α2-adrenergic agonism, imidazolines, and G-protein on insulin secretion in β cells

Hiroshi Hirose, Yoshiko Seto, Hiroshi Maruyama, Katsuaki Dan, Keiko Nakamura, Takao Saruta

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


It is well known that α2-adrenergic agonism inhibits insulin secretion and stimulates glucagon secretion in both animal and human studies. Recently, α2-adrenergic blockers (DG-5128, MK-912, and SL 84.0418) have been studied as antihyperglycemic agents in human subjects. To clarify the action mechanism(s) of these agents, we investigated the effects of α2 agonists and antagonists (10-10 to 10-4 mol/L) and pretreatment by pertussis toxin (PT) on glucose-stimulated insulin secretion using the hamster insulinoma cell line HIT-T15. The imidazoline-derivative α2-adrenoceptor agonists clonidine and oxymetazoline at concentrations as low as 10-8 mol/L significantly inhibited glucose-stimulated insulin secretion by 63% and 65%, respectively (P < .01 for both). These inhibitory effects were abolished by 20-hour preincubation of these cells with PTX 100 ng/mL. The imidazoline- derivative α2-adrenoceptor antagonist DG-5128 at a concentration of 10-4 mol/L doubled insulin secretion with or without pretreatment by PTX (P < .01 for both). Furthermore, both clonidine and oxymetazoline at a high concentration of 10-4 mol/L stimulated insulin secretion with pretreatment of the cells by PTX (P < .05 for both). These results indicate that glucose- stimulated insulin secretion is inhibited by α2-adrenoceptor agonists through PTX-sensitive G-protein in HIT- T15 cells. It is also suggested that imidazoline compounds at high concentrations directly stimulate insulin secretion.

Original languageEnglish
Pages (from-to)1146-1149
Number of pages4
JournalMetabolism: clinical and experimental
Issue number10
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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