Insulin Enhances Epidermal Growth Factor- and Transforming Growth Factor- α-Stimulated Growth in Primary Cultures of Guinea Pig Gastric Mucous Epithelial Cells

Abstract

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.

Transgenic overexpression of Reg protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages

“…These data suggest a new role of Reg protein in the differentiation of gastric progenitor cells along chief cell and parietal cell lineages in vivo. So far, several growth factors have been implicated in the regulation of gastric epithelial cell growth, largely based on studies with cells cultured in vitro (Chen et al, 1991;Rutten et al, 1991Rutten et al, , 1993Yoshiura et al, 1994;Takahashi et al, 1995). Among these growth factors, TGFa is the only one that was shown to exhibit a drastic effect on gastric cell proliferation and differentiation in an in vivo transgenic mouse model Takagi et al, 1992;Sharp et al, 1995).…”

Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

“…The proliferative response of these cells to growth factors might be important in maintaining gastric mucosal integrity and in accelerating peptic ulcer healing. Several growth factors, including epidermal growth factor (EGF), transforming growth factors (TGF-a), insulin, and insulin-like growth factor 1, have been reported to induce a mitogenic response of normal gastric epithelial cells in primary culture (2)(3)(4)(5). Among these factors, the expression of TGF-a has been reported to increase after gastric injury (6) and it is produced by gastric epithelial cells (7).…”

Early Gastrointestinal Regulatory Peptide Response to Intestinal Resection in the Rat Is Stimulated by Enteral Glutamine Supplementation

“…However, in the present study, TGF-α levels in plasma or intestinal mucosa were not significantly affected by resection or nutritional intervention [46]. …”