Huanglian-Renshen-Decoction maintains islet β cell identity in T2DM mice through regulating GLP-1/GLP-1R signaling pathway in both islet and intestine

Abstract Background :This experiment aims to elucidate the effect of HRD on ameliorating diabetes by maintaining islet β cell identity through GLP-1/GLP-1R signaling pathway in both islet and intestine. Methods: After confirming the hypo-glycemic effect of HRD on T2DM mice, the proliferation, apoptosis and transdifferentiation of islet cell were determined by immunohistochemistry and immunofluorescence. Then, the mechanism of HRD improving islet cell identity was verified by Western blot, immunohistochemistry, immunofluorescence and PCR. Results: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time. Moreover, it also increased the number of islet β cell and decreased islet α cell mass. This process is closely related to the transcription factor MafA, PDX1 of the GLP-1/GLP-1R signaling pathway, rather than being produced by proliferation and apoptosis.In further studies, it was found that HRD activated GLP-1/GLP-1R signaling pathway in both islet and intestine. Namely, the levels of GLP-1, GLP-1R, PC1/3, PC2 and other molecules increased significantly. Conclusion: HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to the activation of islet/intestine GLP-1/GLP-1R signal pathway.