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 journalArticle

17 Citations (Scopus)

Abstract

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
Volume46
Issue number10
DOIs
Publication statusPublished - 1997

Fingerprint

Imidazolines
GTP-Binding Proteins
Adrenergic Agents
Insulin
Oxymetazoline
Adrenergic Receptors
Clonidine
L 657743
Glucose
Insulinoma
Adrenergic Antagonists
Pertussis Toxin
Glucagon
Hypoglycemic Agents
Cricetinae
Cell Line

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of α2-adrenergic agonism, imidazolines, and G-protein on insulin secretion in β cells. / Hirose, Hiroshi; Seto, Yoshiko; Maruyama, Hiroshi; Dan, Katsuaki; Nakamura, Keiko; Saruta, Takao.

In: Metabolism: Clinical and Experimental, Vol. 46, No. 10, 1997, p. 1146-1149.

Research output: Contribution to journalArticle

Hirose, Hiroshi ; Seto, Yoshiko ; Maruyama, Hiroshi ; Dan, Katsuaki ; Nakamura, Keiko ; Saruta, Takao. / Effects of α2-adrenergic agonism, imidazolines, and G-protein on insulin secretion in β cells. In: Metabolism: Clinical and Experimental. 1997 ; Vol. 46, No. 10. pp. 1146-1149.
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