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

Marie Amitani,Toshiaki Shimizu,Akio Inui,Timothy Sean Kairupan,Akihiro Asakawa,Nanami Sameshima,Haruka Amitani,Teruto Hashiguchi,Kai-Chun Cheng

doi:10.7717/peerj.1105

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.

Highlights

Allantoin is the primary active compound in yams (Dioscorea spp.) (Sagara et al, 1989)
The present study aimed to identify the role of allantoin in improving damage in pancreatic β-cells induced by a low dose of streptozotocin (STZ)
Allantoin decreased streptozocin-induced cytotoxicity and apoptosis in β-cells Viable β-cells were significantly reduced in the STZ treated group, while cell toxicity and apoptosis were significantly increased compared to the control

Summary

Introduction

Allantoin is the primary active compound in yams (Dioscorea spp.) (Sagara et al, 1989). How to cite this article Amitani et al (2015), Allantoin ameliorates chemically-induced pancreatic β-cell damage through activation of the imidazoline I3 receptors. Several pathogenic processes are involved in the development of diabetes, including the destruction of pancreatic β-cells that results in insulin resistance (Cnop et al, 2005). Autoimmunity is one of the main causes of diabetes type 1 via damage of the insulin-producing β-cells in the pancreas (American Diabetes, 2010). In addition to insulin resistance, increased apoptosis and a significant reduction in the number of β-cells have been implicated in type 2 diabetes (Butler et al, 2003). Prevention of pancreatic damage and the development of therapeutic strategies to protect β-cells have been introduced as a major target for the management of diabetes (Mandrup-Poulsen, 2001)

Methods

Results

Conclusion