Reversible reduction of insulin receptor affinity by ATP depletion in rat adipocytes.
The effects of the metabolic inhibitor NaN3 on insulin receptors in isolated rat fat-cells were investigated. The agent reduced insulin binding in parallel to a decrease of the ATP content of cells. Both effects were observed in the same concentration range of NaN3, and were fully reversible. According to the binding curves the affinity rather than the number of receptors was reduced. Kinetic experiments revealed an increased dissociation rate of the insulin-receptor complex. The effects outlasted cell disruption, since the receptor affinity was still lowered in plasma membranes obtained from NaN3-treated cells. Thus an inhibition of insulin internalization could not account for the observed effects. It is suggested that the observed ATP-dependence of insulin receptor affinity reflects a reversible structural alteration of the receptor, or of some closely related membrane protein.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D012977:Sodium Nitrite / Q000494:pharmacology
D007328:Insulin; D000255:Adenosine Triphosphate; D011972:Receptor, Insulin; D012977:Sodium Nitrite