Journal
DIABETOLOGIA
Volume 44, Issue 4, Pages 480-487Publisher
SPRINGER
DOI: 10.1007/s001250051646
Keywords
aldose reductase inhibitor; protein kinase C; platelet-derived growth factor; diabetic macroangiopathy; oxidative stress
Categories
Ask authors/readers for more resources
Aims/hypothesis. The protein kinase C (PKC), platelet-derived growth factor (PDGF) and polyol pathway play important parts in the hyperproliferation of smooth muscle cells, a characteristic feature of diabetic macroangiopathy. The precise mechanism, however, remains unclear. This study investigated the relation between polyol pathway, protein kinase C and platelet-derived growth factor in the development of diabetic macroangiopathy. Methods. Smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without an aldose reductase inhibitor, epalrestat, or a PKC-beta specific inhibitor, LY333 531. Protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, free cytosolic NAD(+):NADH ratio, the contents of reduced glutathione, and proliferation activities were measured. Results. Smooth muscle cells cultured with 20 mmol/l glucose showed statistically significant increases in protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, and proliferation activities, compared with smooth muscle cells cultured with 5.5 mmol/l glucose. Although epalrestat and LY333 531 inhibited protein kinase C activation induced by glucose to the same degree, the effects of epalrestat on proliferation activities and expression of the PDGF-beta receptor were more prominent than those of LY333 531. Epalrestat improved the glucose-induced decrease in free cytosolic NAD(+):NADH ratio and reduced glutathione content, but LY333 531 did not. The increased expression of membranous PKC-beta II isoform was normalized by epalrestat. Conclusion/interpretation. These observations suggest that polyol pathway hyperactivity contributes to the development of diabetic macroangiopathy through protein kinase C, PDGF-beta receptor, and oxidative stress, and that an aldose reductase inhibitor has a therapeutic value for this complication.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available