Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). The numerous clinical symptoms of DGP and the great cost on the treatment of DGP seriously lowered the patients' life quality. However, the pathogenic mechanism of DGP is still elusive till now. In this study, we aimed to explore the effect of higenamine on the proliferation and apoptosis of gastric smooth muscle cells (SMCs) in DGP rat model. The DGP rat model was built by intraperitoneal injection of Streptozotocin (STZ) into male Sprague-Dawley (SD) rats. Compared with the healthy control group, the level of DGP indicator c-kit was strongly suppressed and the level of Gsα was largely elevated in the STZ-induced model group. By contrast, the addition of higenamine obviously counteracted the effect of STZ on the expression of c-kit and Gsα. Besides that, higenamine improved the decreased emptying ability of the stomach. In addition, the number of gastric SMCs was strongly decreased and cell morphology became irregular in STZ-induced model group. The treatment of higenamine weakened the harm of STZ on the number and morphology of gastric SMCs. Beyond that, higenamine promoted gastric SMCs proliferation and inhibited gastric SMCs apoptosis in DGP model. Further research revealed that higenamine regulated cell proliferation and apoptosis via activating the β2-AR/PI3K/AKT pathway. Taken together, our research revealed that higenamine maintained the survival of gastric SMCs in DGP rat model via the β2-AR/PI3K/AKT pathway, providing a new sight for the treatment of DGP.