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Open Access Research

Allantoin activates imidazoline I-3 receptors to enhance insulin secretion in pancreatic β-cells

Cheng-Chia Tsai1, Li-Jen Chen23, Ho-Shan Niu3, Kun-Ming Chung4, Juei-Tang Cheng5* and Kao-Chang Lin46

Author Affiliations

1 Department of Neurosurgery, Mackay Hospital, and Graduate Institute of Injury Prevention and Control, College of Medicine, Taipei Medical University, Taipei City 10361, Taiwan

2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan

3 Department of Nursing, Tzu Chi College of Technology, Hualien City 97005, Taiwan

4 Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang City, Tainan County 73101, Taiwan

5 Department of Medical Research, Chi-Mei Medical Center, Yong Kang City, Tainan County 73101, Taiwan

6 Institute of Biotechnology, Southern Taiwan University, Tainan City, Yong Kang 71004, Taiwan

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Nutrition & Metabolism 2014, 11:41  doi:10.1186/1743-7075-11-41

Published: 31 August 2014

Abstract

Background

Imidazoline I3 receptors (I-3R) can regulate insulin secretion in pancreatic β-cells. It has been indicated that allantoin ameliorates hyperglycemia by activating imidazoline I2 receptors (I-2R). Thus, the effect of allantoin on I-3R is identified in the present study.

Methods

We used male Wistar rats to screen allantoin’s ability for lowering of blood glucose and stimulation of insulin secretion. Chinese hamster ovary-K1 cells transfected with imidazoline receptors (NISCH-CHO-K1 cells) were also applied to characterize the direct effect of allantoin on this receptor. Additionally, KU14R as specific antagonist was treated to block I-3R in rats and in the cultured pancreatic β-cells named Min 6 cells.

Results

In rats, allantoin decreased blood sugar with an increase in plasma insulin. Also, allantoin enhanced calcium influx into NISCH-CHO-K1 cells in a way similar to agmatine, an I-R agonist. Moreover, KU14R dose-dependently blocked allantoin-induced insulin secretion both in Min 6 cells and in Wistar rats.

Conclusion

Allantoin can activate I-3R to enhance insulin secretion for lowering of blood sugar in Wistar rats. Thus, allantoin may provide beneficial effects as a supplement for diabetic patients after clinical trials.

Keywords:
Allantoin; Insulin secretion; Imidazoline I3 receptor; CHO-K1; NISCH