Allantoin ameliorates chemically-induced pancreatic β-cell damage through activation of the imidazoline I3 receptors.
Objective. Allantoin is the primary active compound in yams (Dioscorea spp.). Recently, allantoin has been demonstrated to activate imidazoline 3 (I3) receptors located in pancreatic tissues. Thus, the present study aimed to investigate the role of allantoin in the effect to improve damage induced in pancreatic β-cells by streptozotocin (STZ) via the I3 receptors. Research Design and Methods. The effect of allantoin on STZ-induced apoptosis in pancreatic β-cells was examined using the ApoTox-Glo triplex assay, live/dead cell double staining assay, flow cytometric analysis, and Western blottings. The potential mechanism was investigated using KU14R: an I3 receptor antagonist, and U73122: a phospholipase C (PLC) inhibitor. The effects of allantoin on serum glucose and insulin secretion were measured in STZ-treated rats. Results. Allantoin attenuated apoptosis and cytotoxicity and increased the viability of STZ-induced β-cells in a dose-dependent manner; this effect was suppressed by KU14R and U73112. Allantoin decreased the level of caspase-3 and increased the level of phosphorylated B-cell lymphoma 2 (Bcl-2) expression detected by Western blotting. The improvement in β-cells viability was confirmed using flow cytometry analysis. Daily injection of allantoin for 8 days in STZ-treated rats significantly lowered plasma glucose and increased plasma insulin levels. This action was inhibited by treatment with KU14R. Conclusion. Allantoin ameliorates the damage of β-cells induced by STZ. The blockade by pharmacological inhibitors indicated that allantoin can activate the I3 receptors through a PLC-related pathway to decrease this damage. Therefore, allantoin and related analogs may be effective in the therapy for β-cell damage.
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Marie
M
Amitani
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Kai-Chun
KC
Cheng
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Akihiro
A
Asakawa
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Haruka
H
Amitani
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Timothy Sean
TS
Kairupan
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Nanami
N
Sameshima
Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Toshiaki
T
Shimizu
Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Teruto
T
Hashiguchi
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Akio
A
Inui
Allantoin; Imidazoline 3 receptor; PLC-related pathway; Pancreatic; Streptozotocin