title: Activation of imidazoline-I3 receptors ameliorates pancreatic damage.
abstract: Agmatine, an endogenous ligand of imidazoline receptors, is reported to exhibit anti-hyperglycaemic and many other effects. It has been established that the imidazoline I3 receptor is involved in insulin secretion. The current study characterizes the role of the imidazoline I3 receptor in the protection of pancreatic islets. The activity effect of agmatine against on streptozotocin (STZ)-induced (5 mmol/L) rat β cell apoptosis was examined by using ApoTox-Glo triplex assay, live/dead cell double staining assay, flow cytometric analysis, and western blot. Imidazoline I3 receptors antagonist KU14R and the phospholipase C inhibitor named U73122 were treated in β cells to investigate the potential signalling pathways. The serum glucose and recovery of insulin secretion were measured in STZ-treated rats after continuously injected agmatine. The apoptosis in rat β cells was reduced by agmatine in a dose-dependent manner, cell viability was improved after treatment with agmatine and these effects were suppressed after the blockade of KU14R and U73122. Western blot analysis confirmed that agmatine could decrease caspase-3 expression and increase the p-BAD levels. In STZ-treated rats, injection of agmatine for 4 weeks may significantly lower the serum glucose and recovery of insulin secretion. This improvement of pancreatic islets induced by agmatine was deleted by KU14R in vivo. Agmatine can activate the imidazoline I3 receptor linked with the phospholipase C pathway to induce cell protection against apoptosis induced by a low dose of STZ. This finding provides new insight into the prevention of early stage pancreatic islet damage.
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Cheng
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asakawa
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Amitani
authors.affiliation: Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takimoto
authors.affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Joshua
authors.initials: J
authors.lastname: Runtuwene
authors.affiliation: Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Inui
keywords: agmatine; apoptosis; beta cell; imidazoline-I3 receptors