Allantoin ameliorates chemically-induced pancreatic beta-cell damage through activation of the imidazoline I3 receptors

作者：Amitani Marie; Cheng Kai Chun; Asakawa Akihiro; Amitani Haruka; Kairupan Timothy Sean; Sameshima Nanami; Shimizu Toshiaki; Hashiguchi Teruto; Inui Akio^*

来源：PeerJ, 2015, 3: e1105.

DOI：10.7717/peerj.1105

• Allantoin
• Imidazoline 3 receptor
• Pancreatic beta-cell
• PLC-related pathway
• Streptozotocin

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 beta-cells by streptozotocin (STZ) via the I3 receptors.
Research Design and Methods. The effect of allantoin on STZ-induced apoptosis in pancreatic beta-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 beta-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 beta-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 beta-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 beta-cell damage.

• 出版日期2015-8-6