Hyperglycemia is known to be a major factor to induce the development of diabetes mellitus. Liver is a very important organ to xenotransplantation and the development of diabetes mellitus. Pig is known to be a most suitable species in transplantation ...
Hyperglycemia is known to be a major factor to induce the development of diabetes mellitus. Liver is a very important organ to xenotransplantation and the development of diabetes mellitus. Pig is known to be a most suitable species in transplantation of human organs. However, the effect of high glucose on cell proliferation in pig hepatocytes was not elucidated. Thus, we examined the effect of high glucose on cell proliferation and its related signal pathways in primary cultured pig hepatocytes. In the present study, high glucose stimulates [³H]-thymidine incorporation. However, mannitol and ʟ-glucose didn't affect [³H]-thymidine incorporation. In addition, high glucose-induced stimulation of [³H]-thymidine incorporation was blocked by PD98059 (a p44/42 mitogen activated protein kinase [MAPK] inhibitor) and 58203580 (a p38 MAPK inhibitor) but not by SP600125 (a SAPK/JNK inhibitor). Indeed, high glucose stimulated p38 MAPK and p44/42 MAPK activation in a time dependent manner. High glucose-induced stimulation of [³H]-thymidine incorporation was blocked by staurosporine, H-7, and bisindolylmaleimide I (protein kinase C [PKC] inhibitors). Indeed, high glucose translocated PKC from cytosolic to membrane fraction. In conclusion, high glucose stimulates cell proliferation via PKC and MAPK activation in cultured pig hepatocytes.