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

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 β-cells. The important findings can be summarized as follows: (i) adipogenesis and early stage β-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 β and duct cells under both conditions, (iv) lipotoxicity induced proliferation of co-cultured β-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 β-cell compensation by stimulating the early stage of β-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.