Tub and β-catenin play a key role in insulin and leptin resistance-induced pancreatic beta-cell differentiation

Publication date: Available online 2 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Merve Ercin, Serap Sancar-Bas, Sehnaz Bolkent, Selda Gezginci-OktayogluAbstractThe aim of this study was to investigate the molecular mechanism of pancreatic islet-derived mesenchymal stem cell (PID-MSC) differentiation into beta-cells in the presence of insulin and leptin resistance stimulators. We determined that beta-cell differentiation was stimulated by glucose, insulin, and leptin. Co-administration of insulin and leptin resulted in greater, at a further stage of differentiation but non-functional beta-cell formation. The levels of p-AKT(Ser473) did not change; SOCS3, PTP1B, p-IRS1(Ser307), PTEN levels increased and p-IRS1(Try) levels decreased due to insulin and leptin co-administration. These findings suggest that co-administration of insulin and leptin to PID-MSCs results in the development of both insulin and leptin resistance together. We showed that this differentiation signaling is mainly mediated by AKT/GSK-3β/β-catenin and Tub. Moreover, β-catenin and Tub were linked to each other in the nucleus under this condition. Furthermore, we found that Tub and β-catenin contributes to insulin production by increasing the expression of transcription factors by binding to the promoter regions of ins1, ins2, and pdx1 genes. In addition, Tub is also bound to the promoter region of the MafA gene. These findings demonstrate that when insulin and...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research