The alteration of renal cell growth is one of the early abnormalities in the diabetic nephropathy. However, effects of high glucose and its action mechanism in the renal proximal tubule cells proliferation have not been elucidated. The effects of 25 mM glucose on cell proliferation, thymidine and leucine incorporation, cell cycle, and lipid peroxides formation were examined in the primary cultured renal proximal tubule cells (PTCs). 25 mM glucose inhibited [3H]-thymidine incorporation and decreased cell growth and contents of S phase in DNA cycle. However, it increased [3H]-leucine incorporation and protein content. Furthermore, 25 mM glucose increased lipid peroxides formation. These hypertropic effects of glucose were blocked by antioxidants, vitamin E, N-acetylcystein, or taurine. Staurosporine and H-7 totally blocked 25 mM glucose-induced lipid peroxides formation and inhibitory effect on [3H]-thymidine incorporation. In addition, high glucose increased secretion of transforming growth factor (TGF)-β1. These effects was also blocked by PKC blockers and antioxidants. In conclusion, high glucose inhibits renal proximal tubule cells proliferation via PKC-oxidative stress-TGF-β1 signaling cascade pathway.
Source: Korean Journal of Physiology & Pharmacology.2000 Oct;4(Suppl):S18-S18
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