The novel effect of Vernicia fordii extract on insulin secretion in pancreatic β-cells and amelioration of insulin resistance in diabetic mice

Abstract

Vernicia fordii Hemsl. (V. fordii), also known as Aleurites fordii, is widely used in oriental medicine to treat wounds and infections. Diabetes is primarily caused by reduced secretion of insulin from pancreatic β-cells. Hence, the restoration of glucose-stimulated insulin secretion (GSIS) in the pancreas is effective therapy for type 2 diabetes. This study aimed to estimate the activity and mechanisms of V. fordii extract (VFE) as an insulin secretagogue and assess its potential as an antidiabetic agent. In pancreatic β-cells, VFE dramatically potentiated insulin release in a dose- & time-response manner and under hyperglycemia compared to euglycemia condition. Interestingly, the insulinotropic role of VFE was blunted by diazoxide and nifedipine. VFE significantly increased glucose uptake and ATP production, and stimulated PKCα/MARCKS activation by intracellular Ca2+ influx. Orally administered VFE ameliorated hyperglycemia and improved insulin sensitivity in HFD-fed mice, and reduced pancreatic islet size compared to that observed in HFD-fed mice. This study establishes that VFE has a strong insulinotropic effect and improves insulin sensitivity by increasing glucose uptake and PKCα activation via intracellular Ca2+ influx. Our study suggests that VFE could be potentially used for improving β-cell function and treating diabetes and metabolic diseases.