These results suggest that phospho-p38MAPK in drug-treated HBlEpC fail to inhibit cyclin E-Cdk2 and cyclin D-Cdk4 activation under hyperglycemic/hyperinsulinemic conditions and long-term exposure to high glucose with insulin overrides the inhibitory effects of activated MAPK-mediated cell cycle arrest in diabetes drug-treated HBlEpC. The gene discussed is CDK4; the disease is diabetes mellitus.