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  2. Allantoin ameliorates chemically-induced pancreatic β-cell damage through activation of the imidazoline I3 receptors

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

  • PeerJ. 2015 Aug 6;3:e1105. doi: 10.7717/peerj.1105.
Marie Amitani 1 Kai-Chun Cheng 1 Akihiro Asakawa 1 Haruka Amitani 1 Timothy Sean Kairupan 1 Nanami Sameshima 1 Toshiaki Shimizu 2 Teruto Hashiguchi 2 Akio Inui 1
Affiliations

Affiliations

  • 1 Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
  • 2 Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
Abstract

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.

Keywords

Allantoin; Imidazoline 3 receptor; PLC-related pathway; Pancreatic; Streptozotocin.

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