HIGH GLUCOSE-INDUCED GROWTH-FACTOR RESISTANCE IN HUMAN FIBROBLASTS CAN BE REVERSED BY ANTIOXIDANTS AND PROTEIN-KINASE C-INHIBITORS

We have studied the influence of high glucose on basal fibroblast prol iferation, growth factor induced cellular proliferation and the effect s of antioxidants, protein kinase C-inhibitors and troglitazone. Fibro blast cultures were obtained from five patients undergoing mammary red uction plastic surgery. A fluorometric method was used for determining total DNA in the cell samples, DNA content being proportional to cell number. D-Glucose at 15.5 mM and above was shown to inhibit fibroblas t proliferation, and the cells were resistant to growth factors such a s IGF-I and EGF at this glucose concentration. H7, bisindolylmaleimide IX, troglitazone, alpha-tocopherol acetate, Q10, ascorbic acid, beta- carotene, DMTU and selenite were all found to reverse the high glucose -induced growth factor resistance observed in human fibroblasts. We be lieve that these findings may be of value in the understanding and fut ure treatment of wound healing in diabetic foot ulcers. (C) 1997 John Wiley & Sons, Ltd.