Abstract
Saponin gypenoside A (GP) has shown its potential to handle diabetes mellitus. MicroRNA-150-3p (miR-150-3p) is closely related to the dysfunction of pancreatic β cells by targeting PDX1. Given the function of GP is related to its regulation on different miRs, the current study assessed the role of miR-150-3p as a therapeutic target for the hypoglycemic effects of GP. Pancreatic β cell dysfunction was induced in mice using the high-fatty diet (HFD) method and then handled with GP. Changes in insulin release and resistance and the activity of the miR-150-3p/PDX1 axis were detected. The expression of miR-150-3p was induced to confirm its central in the effects of GP. The results of in vivo tests were then validated with in vitro assays. HFD administration suppressed glucose tolerance, delayed insulin release, and induced insulin resistance and pancreas apoptosis in mice, which was indicative of the dysfunction of β pancreatic cells. Changes in pancreatic β function were associated with the increased expression of miR-150-3p and suppressed expression of PDX1. After the administration of GP, the impairments of the pancreas were alleviated and the expression of miR-150-3p was inhibited, contributing to the restored level of PDX1. The injection of miR-150-3p agomir counteracted the protective effects of GP. In in vitro assays, the pretransfection of miR-150-3p mimetics also counteracted the protective effects of GP on pancreatic β cells against palmitic acid. Collectively, miR-150-3p played a key role in the protective effects of GP against pancreatic β cell dysfunction by inhibiting PDX1 expression.