miR-375 induces adipogenesis through targeting Erk1 in pancreatic duct cells under the influence of sodium palmitate

Abstract

The goal of this study was to research long-term saturated fatty acid overexposure that can induce differentiation of pancreatic duct cells into adipocytes and also into beta-cells. The important findings can be summarized as follows: (i) adipogenesis and early stage beta-cell differentiation were stimulated in duct cells under lipotoxicity and glucolipotoxicity conditions, (ii) miR-375 expression was upregulated while its target Erk1 was downregulated and miR-375 inhibitor upregulated Erk1 while expression of adipogenesis markers was downregulated in duct cells under both conditions, (iii) apoptosis was induced in beta and duct cells under both conditions, (iv) lipotoxicity induced proliferation of co-cultured beta-cells. These findings suggest that long-term saturated fatty acid overexposure may cause intrapancreatic fat accumulation by inducing differentiation of duct cells into adipocytes and it may contributes to beta-cell compensation by stimulating the early stage of beta-cell differentiation in duct cells. In addition, miR-375 may have the potential to be a new target in the treatment of Type 2 diabetes, and NAFPD due to its role in the adipogenesis of duct cells.