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

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.