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

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

SUBMITTER: Amitani M

PROVIDER: S-EPMC4540048 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Amitani Marie M Cheng Kai-Chun KC Asakawa Akihiro A Amitani Haruka H Kairupan Timothy Sean TS Sameshima Nanami N Shimizu Toshiaki T Hashiguchi Teruto T Inui Akio A

PeerJ 20150806

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 ...[more]

PMID: 26290782

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Dataset Information

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

Publications

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

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