Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose‐induced apoptosis via p21‐p53‐MDM2 signaling in INS‐1 cells

• Published in: Journal of cellular biochemistry Vol. 119; no. 7; pp. 5449 - 5459
• Main Authors: Liu, Rong‐Xing, Ma, Yan, Hu, Xue‐Lian, Liao, Yun‐Peng, Hu, Xiang‐Nan, He, Bai‐Cheng, Sun, Wen‐Juan
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2018
• Subjects: Antidiabetics; Apoptosis; Cyclin-dependent kinase inhibitor p21; Enzyme-linked immunosorbent assay; Glucose; Insulin; Insulin secretion; INS‐1 cells; MDM2 protein; Metformin; p21‐p53‐MDM2; p53 Protein; Pioglitazone; pioglitazone metformin adduct; Secretion; Signal transduction; Signaling; INS-1 cells; apoptosis; insulin secretion; pioglitazone metformin adduct; p21-p53-MDM2
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26701

Pioglitazone/metformin adduct is a novel compound synthesized from pioglitazone and metformin combined at a molar mass ratio of 1:1. The aim of this study was to investigate the effects of pioglitazone/metformin adduct on high glucose‐induced insulin secretion and apoptosis in INS‐1 cells. Western blot and CCK8 analyses showed that the death rate of INS‐1 cells increased in response to glucose treatment in a concentration‐dependent manner. ELISA assays and Western blot analyses showed that insulin secretion peaked following treatment with glucose concentration at 33.33 mM. Treatment of INS‐1 cells with 1 μM pioglitazone/metformin adduct in the presence of 33.33 mM glucose greatly improveded the levels of insulin and apoptosis rates compared to those of the control group. Analysis of mechanism underlying these effects revealed the involvement of the p21‐p53‐MDM2 signaling pathway. Our results indicate that pioglitazone/metformin adduct is superior to pioglitazone and/or metformin in regulating high glucose‐induced insulin secretion and apoptosis in INS‐1 cells. This article provide and validate a new adduct which is effective to insulin secretion and inhibits apoptosis under high‐glucose treatment. It has great value.