Proliferation of immunocytochemically identified islet beta cells in culture: effect of growth factors, hormones, and nutrients.

Immunocytochemically identified, differentiated, single beta-cells proliferate to form colonies, which then grow into hillocks and islets. Beta-Cell proliferation is most easily quantified during the first week, when colonies are forming. The experimental objective was stimulation of beta-cell proliferation by culture medium supplementation with growth factors, hormones, or nutrients. We found that beta-cell proliferation is stimulated by iron-saturated transferrin, interleukin-1-alpha, fetal calf serum, and glucose. In response to transferrin, proliferation of beta-cells is progressively stimulated, reaching a maximum at 30 micrograms/ml. At greater concentrations the stimulatory effect is progressively lost. Interleukin-1-alpha maximally stimulates beta-cell proliferation at 10 pg/ml, regresses to control levels at 10(3) pg/ml, and inhibits proliferation progressively at greater concentrations. Fetal calf serum maximally stimulates beta-cell proliferation at concentrations of 10%, and glucose stimulates maximally at 15 mM concentrations. The proliferative response to transferrin, interleukin-1-alpha or glucose is serum dependent. Serum and transferrin synergistically stimulate glucose-induced beta-cell proliferation. Interleukin-1-beta, interleukin-2, rat growth hormone, and rat prolactin fail to stimulate beta-cell proliferation.