IGF1 and Hyperglycemia: Karnevi et al. [19] reported that metformin can significantly reduce the proliferation of several pancreatic cancer cell lines under normal glucose conditions; however, they found that hyperglycemia reduced metformin-induced growth inhibition by enhancing the IGF-I response and activating AKT, which stimulated AMPK-Ser485 phosphorylation and impaired AMPK-Thr172.