Objective:To clarify the effect of glucose on peritoneal sclerosis, we perf
ormed several experiments to determine how glucose influences the prolifera
tion of, and the production of extracellular matrix proteins by, peritoneal
fibroblasts. The effect of heparin on these phenomena was also studied.
Design: Using rat peritoneal fibroblasts, cells were cultured in four separ
ate media: M199 with 5% fetal bovine serum (FBS) (control medium), control
medium with 4% glucose (glucose medium), glucose medium with H7 [an inhibit
or of protein kinase C (PKC)]50 mu mol, and glucose medium with heparin 50
mu g/mL. Cell proliferation and concentrations of procollagen 3 peptide (P3
P) and hyaluronic acid (HA) in the supernatants were evaluated at 24 hours,
72 hours, and 120 hours after culture. PKC activity in cytosolic and cell
membrane fractions were measured 30 minutes after incubation in control med
ium and in glucose medium with and without heparin.
Results: Glucose accelerated cell proliferation 24 hours after culture, but
inhibited it 120 hours after culture. Glucose stimulated the production of
HA from these cells 72 hours and 120 hours after culture, but it did not s
timulate the production of P3P at any time. Heparin and H7 inhibited cell p
roliferation by glucose 24 hours after culture. Heparin and H7 also inhibit
ed the production of HA in the peritoneal fibroblasts after culture, but di
d not affect the production of P3P. Glucose accelerated PKC activity in cel
l membrane, but not in cytosol. Heparin inhibited the elevated PKC activity
of the membrane fraction by glucose.
Conclusion: Glucose may accelerate the proliferation of, and HA production
in, peritoneal fibroblasts by stimulation of cellular PKC activity. Heparin
suppresses these phenomena by inhibiting PKC activity.