Maternal Low Protein Isocaloric Diet Suppresses Pancreatic β-Cell Proliferation in Mouse Offspring via miR-15b

The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low-protein (LP) isocaloric diet induced pancreatic beta-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for beta-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased beta-cell mass and insulin secretion. Reduction in the beta-cell proliferation rate and cell size contributed to the decreased beta-cell mass. MiR-15b was up-regulated in the islets of LP offspring. The up-regulated miR-15b inhibited pancreatic beta-cell proliferation via targeting cyclinD1and cyclin D2. Inhibition of miR-15b in LP islet cells restored beta-cell proliferation and insulin secretion. Our findings demonstrate that miR-15b is critical for the regulation of pancreatic beta-cells in offspring of maternal protein restriction, which may provide a further insight for beta-cell exhaustion originated from intrauterine growth restriction.