Relationship between increased binding and insulin-like effects of human growth hormone in adipocytes from young fa/fa rats.
Binding and insulin-like effects of human GH (hGH) in inguinal adipocytes from young lean Fa/fa and obese fa/fa Zucker rats were studied. The binding of [125I]hGH per unit surface area is 2-fold higher in adipocytes prepared from 16- and 30-day-old fa/fa rats than in cells from lean littermates. A 3-h preincubation of the cells increases the hGH-binding capacity without changing the affinity of the binding, regardless of genotype. Freshly isolated adipocytes from 30-day-old lean rats fail to respond to hGH, whereas after preincubation of the cells, hGH produces a maximal 105% increase in glucose transport and a maximal 40% increase in glucose oxidation. In contrast, freshly isolated adipose cells from fa/fa rats are already responsive to hGH and the amplitude of the response is markedly elevated in preincubated cells, with a 430% stimulation of glucose transport. The concentration of hGH (1 nM) that inhibits 50% of [125I]hGH binding and that which produces half-maximal stimulation of glucose transport as well as glucose metabolism are not different, suggesting the absence of spare receptors for these insulin-like effects of hGH. Plots of GH effects on glucose transport as a function of receptor occupancy are linear, with a change in the slope after preincubation. Our results suggest a strong correlation between binding of hGH and actions on glucose transport and glucose metabolism in adipocytes of young Zucker rats.
Landron
D
D
Unité de Biologie et Pathologie de la Croissance et du Développement, INSERM U.30, Hôpital des Enfants-Malades, Paris, France.
Guerre-Millo
M
M
Postel-Vinay
M C
MC
Lavau
M
M
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D002469:Cell Separation; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains / Q000378:metabolism*; D011924:Rats, Zucker
D007328:Insulin; D013006:Growth Hormone; D005947:Glucose