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 proliferation, growth factor induced cellular proliferation and the effects of antioxidants, protein kinase C-inhibitors and troglitazone. Fibroblast cultures were obtained from five patients undergoing mammary reduction 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 fibroblast proliferation, and the cells were resistant to growth factors such as 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 believe that these findings may be of value in the understanding and future treatment of wound healing in diabetic foot ulcers.
Hehenberger
K
K
Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden. karin.hehenberger@molmed.ki.se
Hansson
A
A
D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D014945:Wound Healing / Q000502:physiology
D000975:Antioxidants; D002839:Chromans; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases; D000077288:Troglitazone; D005947:Glucose