Identification active compounds from Dregea volubilis that improve insulin secretion by regulating pancreatic β

Abstract

Type 2 diabetes (T2D) occurs due to a lack of insulin secretion by glucose stimulation, so high blood glucose levels predominate that associated with metabolic dysregulation. The exploration of bioactive compounds from natural sources has attracted considerable attention because these molecules provide chemically diverse scaffolds with broad pharmacological potential and have historically contributed to the successful development of numerous clinically approved drugs. In this study, we examined the effect of compounds isolated from Dregea volubilis (L.f.) Benth. ex Hook. f. (Apocynaceae) on glucose‐stimulated insulin secretion (GSIS) from the pancreatic β ‐cells. 17 β ‐Marsdenin ( 1 ), drevoluoside N ( 2 ), and dreageoside A11 ( 3 ) were screened for their ability to increase GSIS using a rat insulin ELISA kit. Western blotting was used to investigate the levels of pancreatic and duodenal homeobox‐1 (PDX‐1), phosphorylation of insulin receptor substrate‐2 (P‐IRS‐2), phosphorylation of phosphatidylinositol 3‐kinase (P‐PI3K), and phosphorylation of Akt (P‐Akt), which are related to β ‐cell function and insulin secretion in INS‐1 cells. Compounds 1 – 3 stimulated insulin secretion in INS‐1 cells without inducing cytotoxicity. A further experiment showed that compound 3 enhanced the expressions of PDX‐1, P‐IRS‐2, P‐PI3K, and P‐Akt in INS‐1 cells. The data suggest that compounds 1 – 3 from D. volubilis have the potential to improve insulin secretion in β ‐cells, representing the first step toward the development of potent antidiabetic drugs.