The key regulation of LncRNA MALAT during reprogramming of primary mouse hepatocytes into insulin producing cells.

Generating insulin-producing cells (IPCs) poses a significant hurdle in diabetes cell therapy. The liver is an advantageous cell source for pancreatic cell production due to its similar origin, potent proliferation, and regeneration capabilities, and shared glucose-sensing system. Hence, it is crucial to further comprehend the molecular regulatory mechanism of liver cell reprogramming into IPCs to refine the induction protocol and boost the induction efficiency. The expression of LncRNA MALAT1 and PI3K was elevated, in contrast to a significant diminution in miR-124-3p expression, during the progression of in vitro induced differentiation of primary mouse hepatocytes. In the overexpression group of lncRNA MALAT1 transfected, the level of PI3K diminished considerably during the IPCs induction phase, Consequently, effects on differentiation into IPCs were diminished in mice primary hepatic cells. Furthermore, the in vitro responsiveness of primary mouse hepatocytes-derived β islet-like cells to high glucose stimuli and insulin release by these cells were significantly diminished in the overexpression of lncRNA MALAT1 transfection group, while the outcomes were converse in the si-lncRNA MALAT1 group. And the transplanted IPCs(Si-MALAT1) have better cell function in T1DM mice. The experimental findings suggest that transfection of lncRNA MALAT1 alters the expression levels of miR-124-3p and PI3K genes in the final IPCs phase, accomplishing regulation of primary mouse hepatocytes directed β islet-like cell differentiation efficiency.