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Cu++-dependent Thiol Stimulation of Glucose Metabolism in White Fat Cells

1972; Elsevier BV; Volume: 247; Issue: 19 Linguagem: Inglês

10.1016/s0021-9258(19)44785-6

1083-351X

Michael Czech, John N. Fain,

Advanced Glycation End Products research

Abstract EDTA, added either alone or with equimolar concentrations of CaCl2 or MgCl2, was without effect on the increase in fat cell glucose oxidation due to insulin, vitamin K5, menadione, or sucrose hyperosmolarity. In contrast, EDTA markedly inhibited the action of cysteine, glutathione, and an insulin-like factor from serum on fat cell glucose metabolism. The inhibition by EDTA was greater on high concentrations of cysteine (1.5 or 2 mm) than lower concentrations (0.5 or 1 mm). In fat cells incubated in a 3% albumin medium which had been incubated for 30 min with 2 mm cysteine prior to addition of EDTA and cells, EDTA was ineffective in blocking the action of cysteine. The stimulation by cysteine, glutathione, and vitamin K5 of white fat cell glucose oxidation was inhibited in the absence of albumin while the response to insulin or sucrose hyperosmolarity was unaffected. The effect of albumin on the action of cysteine was biphasic. The stimulatory effect of 0.05 or 0.5 mm cysteine was about 3-fold greater than 1.5 mm cysteine in the presence of 0.75% albumin while with 3% albumin present the response of cells to 1.5 and 0.5 mm cysteine was maximal and that to 0.05 mm cysteine was nearly abolished. Dialysis of albumin reduced its ability to support the effect of cysteine as did passage over Sephadex G-50. The stimulation by cysteine and glutathione of glucose metabolism was inhibited by almost 90% if fat cells were incubated in albumin which had been exposed to 3.3 mm phenanthroline and then chromatographed on Sephadex G-50 while the increase due to insulin was diminished by only 25%. Cu++ at 3 x 10-6 and 10-5 m, but not 10-4 m, restored the stimulatory effect of cysteine on fat cell glucose metabolism in the presence of the phenanthroline, Sephadex-treated albumin. These results indicate that the stimulatory effects of cysteine on white fat cell glucose utilization involve a mechanism dependent on the presence of divalent copper.