Physiological concentrations of insulin augment pancreatic cancer cell proliferation and glucose utilization by activating MAP kinase, PI3 kinase and enhancing GLUT-1 expression.

摘要: Pancreatic carcinoma is characterized by poor prognosis and lack of response to conventional therapy for reasons that are not clear. Because the structural relationship between exocrine endocrine pancreas high concentrations islet hormones bathing pancreatic tissue, we hypothesized cancer cell proliferation glucose utilization regulated hormones, particularly insulin. Based on this, effect cells in vitro was investigated. Five lines, CD11, CD18, HPAF, PANC-1, MiaPaCa2 were used investigate proliferation, utilization, GLUT-1 expression. Insulin, but somatostatin glucagon, induced growth a concentration- time-dependent manner. At within range those intrapancreatic vasculature, insulin (10(-10)-10(-8) mol/L) markedly increased [3H]-thymidine incorporation. Insulin significantly enhanced before it proliferation. The MAPK kinase inhibitor PD 098059 abolished insulin-stimulated DNA synthesis partially reduced uptake. In contrast, PI3 wortmannin substantially inhibited insulin-induced uptake blocked thymidine Furthermore, after 24-hour treatment with insulin, GLUT-I expression increased, indicating enhances partly through increasing transport. These findings suggest stimulates two distinct pathways. augments mainly MAP activation enhancement High likely play an important role stimulating indirectly substrate availability as well direct action trophic factor.