Proliferation of Immunocytochemically Identified Islet Beta Cells in Culture

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Abstract
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 .mu.g/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 103 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.

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