4-Methylcatechol stimulates apoptosis and reduces insulin secretion by decreasing betacellulin and inhibin beta-A in INS-1 beta-cells

Abstract

Insulinoma INS-1 cell line is a pancreatic beta cell tumor which is characterized with high insulin content and secretion in response to increasing glucose levels. 4-Methylcatechol (4-MC) is a metabolite of quercetin, which is known as a potential drug for inhibition of tumorigenesis. The aim of this study was to determine the applying doses of 4-methylcatechol (4-MC) for triggening cell death and decreasing the cell function of rat insulinoma INS-1 beta cells. The rate of apoptosis and the amount of insulin in the cell and the secretions were determined by the ELISA method. Betacellulin (BTC) and inhibin beta-A amounts in both the cell and the glucose induced secretion were investigated by Western blotting. Furthermore, BTC, Inhibin beta-A, Ins1, Ins2, and GLUT2 gene expression levels were determined by the by the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. We noted a significant decrease in cell viability, while an increase in apoptotic cell death by 4-MC treatment. It caused a decrease in the secretion of BTC, expressions of both BTC and inhibin beta-A. We showed a decrease in the expressions of Ins1 and GLUT2, while there is no alteration in the level of insulin protein. Insulin secretion levels increased in INS-1 cells given 4-MC by basal glucose concentration while they did not response to high concentration of glucose, which indicates that 4-MC disrupts the functionality of INS-1 cells. These results revealed that 4-MC induces apoptosis and decreases insulin secretion by reducing BTC and inhibin beta-A in insulinoma INS-1 cells. Thus, 4-MC may be offered as a potential molecule for treatment of insulinoma.

Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules

“…Clostridium_ Symbiosum decreased significantly after treatment, and its negatively related FAHFA (Fatty acid esters of hydroxy fatty acids) has anti-inflammatory effect and can inhibit the production of LPS induced pro-inflammatory cytokines in macrophages and dendritic cells ( Yore et al., 2014 ). Erysipelatoclostridium_ Ramosum that reduced after treatment was negatively correlated with LAP (plasma lysophosphatidic acid) and 4_ Methylcatechol, both of which could promote tumor cell apoptosis ( Zheng et al., 2004 ; Karatug Kacar et al., 2018 ). In patient case 2, Streptoccus_ Parasanguinis and dialist_ Pneumosintes decreased after treatment and were negatively correlated with 13(S)-HOTrE which can produce anti-inflammatory effect by inactivating NLRP3 inflammatory body complex ( Kumar et al., 2016 ).…”

Investigation of cell death mechanism and activity of esculetin-loaded PLGA nanoparticles on insulinoma cellsin vitro

“…This evidenced that the cells have not been biologically changed. The experimental results are shown in our previous study . The INS‐1 cells between passages 2–9 were used for experiments in our previous study.…”