Effects of growth hormone on glucose metabolism and glucose transport in 3T3-F442A cells: dependence on cell differentiation.

Abstract

In differentiated adipocytes of the 3T3-F442A cell line, 4-h incubation with human GH transiently stimulates glucose oxidation and lipid accumulation. When the incubation is extended to 48 h, hGH suppresses these indicators of glucose metabolism. The stimulation of glucose oxidation or lipid accumulation required a period of serum deprivation before incubation with GH, while the later inhibitory effect of GH occurred equally well whether or not cells were serum-deprived. Since the 3T3-F442A adipocytes differentiate in culture from preadipocyte fibroblasts, we examined the importance of the state of differentiation on metabolic responses to GH. GH had no reproducible effect on glucose oxidation after 4 or 48 h in the preadipocyte fibroblasts. To determine whether the effects of GH on glucose metabolism involved changes in glucose transport, the uptake of a low concentration (558 nM) of [14C]glucose was measured in the adipocytes. Glucose uptake increased 2- to 4-fold after 5-15 min of incubation with GH. This rapid response peaked in 15-30 min and subsided by 120 min despite the continued presence of GH. After 24 h of incubation with GH, glucose uptake was inhibited. In preadipocytes, GH occasionally stimulated glucose uptake in a transient manner. When present, the stimulation was generally of lesser magnitude and shorter duration than in the adipocytes. No inhibition of glucose uptake was observed in the preadipocytes after 24 h of incubation. These differences in responsiveness of the preadipocytes compared to the adipocytes cannot be attributed to differences in receptor binding or detectable differences in GH receptor type or size, as determined by migration of [125I]iodohuman GH-receptor complexes in electrophoretic gels. These findings indicate that GH rapidly alters glucose uptake in 3T3-F442A adipocytes. The changes in glucose uptake most likely play a major role in the GH-induced changes in the conversion of glucose to lipid and CO2 observed previously. These metabolic responses to GH are dependent on the adipose conversion of the 3T3-F442A cells. As the 3T3-F442A cells express the adipocyte phenotype, development of increased metabolic regulation by GH appears to require changes in postbinding or postreceptor phenomena.