Insulin enhances epidermal growth factor- and transforming growth factor-alpha-stimulated growth in primary cultures of guinea pig gastric mucous epithelial cells.
The effect of insulin on epidermal growth factor (EGF)- and transforming growth factor-alpha (TGF alpha)-induced cell proliferation was examined in primary cultures of gastric surface mucous epithelial cells by using changes in cell counts and DNA as indices of cell growth. With 1.0% fetal bovine serum and Dulbecco's modified Eagle medium (low-serum DMEM) there was no effect of bovine insulin (0.1-10.0 micrograms/ml) on cell growth. Higher doses of insulin (20.0 micrograms/ml) in low-serum DMEM were able to stimulate growth of these cells compared with controls. In low-serum DMEM with no insulin the lowest effective dose of EGF or TGF alpha for stimulating cell growth was 10 nM and 5 nM, respectively. In low-serum DMEM containing 2.5 micrograms/ml insulin there was a dose-dependent increase in cell growth with EGF and TFG alpha at concentrations of 0.5-10.0 nM. The addition of insulin alone at 2.5 micrograms/ml, EGF alone at 2 nM, or TGF alpha alone at 2 nM in serum-free DMEM media had no effect on gastric surface mucous cell DNA. In serum-free DMEM media with 2.5 micrograms/ml insulin, the addition of 2 nM EGF or 2 nM TGF alpha caused an increase in both cell counts and DNA of 1.80- and 3.50-fold, respectively. The present study demonstrates that insulin, at concentrations that are not mitogenic, will enhance the proliferative effects of EGF and TGF alpha on the growth of primary cultures of guinea pig gastric surface mucous epithelial cells.
Rutten
M J
MJ
Medical Research Service, Dept. of Veterans Affairs Medical Center, Kansas City, Missouri 64128.
Harmon
P
P
Campbell
D R
DR
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D003470:Culture Media / Q000592:standards; D016895:Culture Media, Serum-Free / Q000592:standards; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000187:drug effects* / Q000502:physiology; D004848:Epithelium / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects*; D006168:Guinea Pigs; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000187:drug effects* / Q000502:physiology
D003470:Culture Media; D016895:Culture Media, Serum-Free; D007328:Insulin; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D004247:DNA