Dexamethasone permits the release of an inhibitor of pyruvate dehydrogenase from Reuber H-35 hepatoma cells in response to insulin.

Reuber H-35 rat hepatoma cells respond to physiological levels of insulin as a growth factor. Glucocorticoids antagonize this response. A chemical mediator of insulin action which activates mitochondrial pyruvate dehydrogenase has also been isolated from these cells. The present report demonstrates that if the H35 cells are incubated with glucocorticoid before treatment with insulin, they produce not only the stimulator, but also inhibitory mediator. Cells exposed to the glucocorticoid but not to insulin do not produce the inhibitory mediator. Therefore, insulin interaction with the cell is necessary to elicit this negative modifier of pyruvate dehydrogenase. A time course of the response suggests that the effect of the glucocorticoid is time dependent. The inhibitory mediator can be separated from the stimulatory mediator by molecular sieve chromatography. These results suggest a biochemical basis for glucocorticoid-mediated insulin resistance.