Premium
Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose‐induced apoptosis via p21‐p53‐MDM2 signaling in INS‐1 cells
Author(s) -
Liu RongXing,
Ma Yan,
Hu XueLian,
Liao YunPeng,
Hu XiangNan,
He BaiCheng,
Sun WenJuan
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26701
Subject(s) - pioglitazone , metformin , medicine , apoptosis , endocrinology , insulin , western blot , chemistry , secretion , adduct , biology , diabetes mellitus , type 2 diabetes , biochemistry , gene , organic chemistry
Abstract 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.