Glucocorticoids enhance glucose uptake and affect differentiation and beta-adrenergic responsiveness in muscle cell cultures

Abstract

The role of glucocorticoids (GLC) in liver glycogen metabolism is well characterized; its role in peripheral tissues is not as well understood (Baxter, 1976). GLC administration in vivo is associated with hyperglycemia, but it is not clear whether decreased glucose uptake in a peripheral tissue like muscle accounts, in part, for the effect. We investigated the relationship of glucose uptake to β-adrenergic responsiveness in muscle cell cultures exposed to GLC. Under these conditions GLC and other serum factors are present in at least a tenfold dilution relative to in vivo conditions. We observed that the GLC dexamethasone (DEX) induces a significantly enhanced V max for deoxyglucose uptake in the rat muscle cell lines L 8 (200–400%) and L 6E 9 (50–100%). DEX inhibits cell fusion and promotes epithelioid morphology within the effective dose range ( L 8 > L 6 E 9). Growth is slightly enhanced (10–20%) at 0.1–1.0 μM. In these cells DEX also inhibits intracellular β-adrenergic-sensitive cyclic AMP accumulation and reduces basal, catecholamine-sensitive and fluoride-sensitive adenylate cyclase in cell homogenates. The effects of DEX on deoxyglucose uptake and β-adrenergic responsiveness are both dose (1 nM—0.1 nM) and time (1–3 days) dependent, and reversible. The degree of inhibition of the β-adrenergic system seems to be directly related to the degree of enhancement of deoxyglucose uptake. These observations suggest that the action of DEX on muscle cell glucose uptake is related to its effect on the β-adrenergic system.