Glucocorticoids enhance glucose uptake and affect differentiation and beta-adrenergic responsiveness in muscle cell cultures.
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 beta-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 Vmax for deoxyglucose uptake in the rat muscle cell lines L8 (200--400%) and L6E9 (50--100%). DEX inhibits cell fusion and promotes epithelioid morphology within the effective dose range (L8 greater than L6E9). Growth is slightly enhanced (10--20%) at 0.1--1.0 microM. In these cells DEX also inhibits intracellular beta-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 beta-adrenergic responsiveness are both dose (1 nM--0.1 nM) and time (1--3 days) dependent, and reversible. The degree of inhibition of the beta-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 beta-adrenergic system.
D000262:Adenylyl Cyclases / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D003847:Deoxyglucose; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose