Contribution of the Long Non-Coding RNA H19 to Neonatal and Adult Rodent β-Cell Mass Expansion.

Pancreatic β-cell expansion throughout the neonatal period is essential to generate the appropriate mass of insulin-secreting cells to maintain blood glucose homeostasis later in life. Hence, defects in this process can predispose to diabetes development at adulthood. Global profiling of the transcripts in pancreatic islets of newborn and adult rats revealed that the expression of the long non-coding RNA H19 is controlled by the transcription factor E2F1 and is profoundly downregulated during the post-natal period. H19 silencing decreased newborn β-cell expansion while its re-expression promoted proliferation of adult β-cells via a mechanism involving the microRNA let-7 and the activation of Akt. The offspring of rats kept on a low protein diet during gestation and lactation display a reduced β-cell mass and an increased risk to develop diabetes at adulthood. We found that the islets of newborn rats born from dams on a low protein diet express lower levels of H19. Moreover, we observed that H19 expression raises in the islets of obese mice under conditions of increased insulin demand. Taken together, our data suggest that the lncRNA H19 plays an important role in postnatal rat β-cell mass expansion and contributes to the mechanisms compensating for insulin resistance under obesity conditions.