Isoproterenol reduces insulin stimulation of hexose uptake by rat adipocytes via a postinsulin binding alteration.
The present studies have investigated the acute changes previously reported in insulin binding and insulin action that occur in fat cells after a 30-min treatment with isoproterenol. We find that the marked reduction in high affinity insulin binding can be explained by a drop in the pH of the incubation medium from 7.4 to 6.9, a change associated with the accelerated production of FFA. The alteration in insulin binding may explain the rightward shift in the insulin dose response for the stimulation of glucose transport. When the incubation medium is modified to prevent the pH change, isoproterenol stimulation fails to reduce insulin binding. In addition, the tyrosine kinase activity of the insulin receptor isolated from isoproterenol-treated cells is not altered, at least as measured by the phosphorylation of tyrosine residues on the artificial substrate, Glu80Tyr20. There are, however, changes produced in the insulin stimulation of 2-deoxy-D-glucose uptake. The response of the cells to a maximum effective concentration of insulin is reduced 35% by a 30-min treatment with 0.1 microM isoproterenol. This change occurs in parallel with a moderate rightward shift in the insulin dose-response curve. Thus, isoproterenol treatment rapidly alters the ability of the adipocyte hexose transport system to respond to insulin, but the responsible alteration(s) is located beyond the insulin-binding site and possibly beyond the insulin receptor itself.
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004822:Epididymis; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism
D003837:Deoxy Sugars; D007328:Insulin; D003847:Deoxyglucose; D000242:Cyclic AMP; D011972:Receptor, Insulin; D007545:Isoproterenol