Loureirin B promotes insulin secretion through GLP-1R and AKT/PDX1 pathways

Abstract

Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated a diabetic model in mice with LB, and the results showed that LB lowered blood glucose and alleviated islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated mice with LB in a diabetic model and showed that LB lowered blood glucose and reduced islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Further, after inhibiting GLP-1R activity, the results showed that LB promoted insulin secretion, Ins-1 cell proliferation and reduced Ins-1 cell apoptosis with reduced effect, indicating that LB achieved the above effects by activating GLP-1Ra. Meanwhile, cellular cAMP levels increased when GLP-1R was overexpressed, which also demonstrated the interaction between LB and GLP-1R. Subsequently, the effect of LB on cellular potassium channels was examined by membrane clamp, and the results showed that LB increased intracellular Ca2+ concentration and stimulated insulin secretion by activating GLP-1R and thus closing the ATP-sensitive potassium channels. On the other hand, the activation effect of LB on AKT/PDX1 signaling pathway was verified.