CDKN1B and Hyperglycemia: Although the mechanism of action of the synergistic effect of hyperglycemia and p27Kip1 silencing on adult islet beta cell replication is not yet clear, we hypothesize that the persistent suppression of p27Kip1 by lentivirus-carrying shRNA on adult islet cells will drive more cells into the G1/S phase and the high glucose-mediated persistent elevation of cyclin B1 will prepare more cells to be ready to enter mitosis and increase beta cell replication.