Identification of a novel insulin receptor-binding protein from Momordica charantia by transcriptomic, proteomic, and docking analyses

ABSTRACT: Momordica charantia (MC) is a common vegetable in tropical areas and has been used for a long time as an alternative therapy for diabetes. Although several constituents of MC have displayed the hypoglycemic effects, the hypoglycemic targets of these constituents remain to be clarified. In this study, we analyzed and elucidated the therapeutic targets contributing to the hypoglycemic effect of aqueous extract of MC seeds (MCSE) by transcriptomic analysis. The protein ingredients aimed at the hypoglycemic target were further identified by proteomic, docking, and receptor-binding assays. Our data showed that MCSE, which was rich in small-molecular weight proteins, displayed hypoglycemic effects in normal and diabetic mice by glucose tolerance assay. MCSE significantly and primarily regulated the insulin signaling pathway in muscles and adipose tissues, suggesting that MCSE might target to insulin receptor (IR), stimulate the IR-downstream pathway, and subsequently display the hypoglycemic activity. We further identified that inhibitor against trypsin (TI) of MC directly docked into IR and activated the kinase activity of IR. In conclusion, our findings suggested that MCSE regulated glucose metabolism mainly via insulin signaling pathway. Moreover, we newly identified that TI was a novel IR-binding protein of MC that triggers the insulin signaling pathway via binding to IR. Mice were fasted for 4 h and MCSE or PBS was then orally given 15 min before intraperitoneal administration of glucose solution (1 g/kg body weight). Blood samples were collected from tails at 15 min before and at 15, 30, 60, 90, 120, 150, 180, and 240 min after glucose challenge. Blood glucose was measured by glucose oxidase method using a glucometer (ACCU-CHEK Advantage, Roche Diagnostics, Basel, Switzerland). Mice were sacrificed 4 h after glucose challenge. Muscles, adipose tissues, and livers were collected for microarray analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Chien-Yun Hsiang 

PROVIDER: E-GEOD-39689 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress