RT Journal Article SR Electronic T1 Insulin Does Not Augment In Vitro Tumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner JF bioRxiv FD Cold Spring Harbor Laboratory SP 169664 DO 10.1101/169664 A1 Tao Liao A1 Xiao-Hui Li A1 Yan-Ping Chen A1 Li-Li Tan A1 Ji-Da Zhang A1 Xin-An Huang A1 Qin Xu A1 Sui-Qing Huang A1 Chang-Qing Li A1 Qing-Ping Zeng YR 2017 UL http://biorxiv.org/content/early/2017/07/28/169664.abstract AB Background Whether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).Methodology/Principle Findings We cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated by NOS2 knockdown.Conclusions/Significance Cellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.