Evidence for the autocrine inhibition of glycolysis in human fibroblasts.

We investigated the mechanism by which glucose refeeding can reverse the enhancement of glycolysis caused by glucose starvation. Human fibroblasts were deprived of glucose for 18 hr and then refed for 1 hr with either (a) medium from sister glucose-starved cultures (controls), (b) fresh, glucose-containing medium (fresh medium), or (c) medium conditioned for 18 hr by glucose-fed cells (conditioned medium). Despite a lower glucose content, conditioned medium was significantly more effective at inhibiting the accumulation of radio-labeled glucose than fresh medium (74 vs. 49% inhibition). The uptake of 2-deoxyglucose was not affected by either medium, indicating that the site of control of glycolysis was distal to glucose transport and phosphorylation. The active principle was heat labile, dialyzable (Mr less than 12,000) and unrelated to the lactate content of conditioned medium. Medium conditioned by cells exposed to 3-O-methylglucose did not inhibit glycolysis in glucose-starved cells even though long-term exposure to this hexose, like glucose, results in the repression of transport.