Rapamycin suppresses hypoxia/reoxygenation-induced islet injury by up-regulation of miR-21 via PI3K/Akt signalling pathway.

Objectives: Increasing evidences indicate that microRNAs may play a critical role in the regulation of hypoxia/ reoxygenation (H/R) injury, and their expression is associated with mTORC activity.We propose that rapamycin modulates H/R-induced islets injury by regulating microRNA expression. Materials and methods: We investigated whether rapamycin treatment could alter the expression profile of miRNAs in islets. Furthermore, we assessed the islet apoptosis and function after H/R or syngeneic islet transplantation. Results: We found that rapamycin treatment significantly decreased H/R-induced islet apoptosis, and improved islet function in vivo and in vitro, and that miR-21 gene transcription is controlled by rapamycin.When the PI3k/Akt signalling pathways was blocked by wortmannin, the up-regulative effects of rapamycin on miR-21 expression were inhibited in vitro. Furthermore, our study clearly demonstrates that miR-21 is essential for the rapamycin-mediated protection islets against H/R injury. Discussion: Our findings indicate that up-regulation of miR-21 function in islets by treatment with rapamycin or overexpression of the miR-21 could represent a potential new therapy for the treatment of H/R injury. Conclusion: The results of this study clearly suggest that rapamycin exerts its inhibitory effects on islets H/R injury by inducing miR-21 expression via PI3K/Akt.