Effect of Insulin on the Conversion of Glucose-C-14 to C-14-02 by Normal and Diabetic Fibroblasts in Culture

作者：Samuel Goldstein, John W. Littlefield · 发表于：Diabetes · 年份：1969 · DOI：10.2337/diab.18.8.545 · 被引用次数：63 · 研究领域：Pancreatic function and diabetes、Metabolism, Diabetes, and Cancer、Diabetes Treatment and Management

In an attempt to elucidate the basic genetic defect (s) in diabetes, the acute effect of insulin on the conversion of glucose-C-14 to C-14-02 in cultured human diploid fibroblasts was measured under various conditions. Freshly trypsinized cells did not respond to insulin, but after more than sixteen hours in growth medium, a small but significant stimulation, requiring high concentrations of insulin (0.26 U. per ml.) was observed. Stimulation by insulin in various normal strains ranged from 5 to 45 per cent with a mean of 18 per cent (p < .001). C-14-O2 production was approximately linear with time after an initial lag phase and proportional to the number of cells inoculated. Increasing the concentration of glucose in the medium increased C-14-O2 production, with stimulation by insulin apparent at only very low concentrations and at 250 mg. per 100 ml., the highest concentration studied. Experiments comparing the oxidation of glucose-l-C-14 versus glucose-6-C-14 showed that substantial C-14-O2 production occurred via the hexose monophosphate shunt, but that most of the increase in C-14-O2 production in the presence of insulin occurred via the Krebs cycle. A comparison of basal and insulin-stimulated C-14-O2 production in normal and diabetic fibroblasts revealed no significant differences. Possible explanations for the failure to distinguish between the two groups are discussed.