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Coupling of insulin receptors to glucose transport a temperature dependent time lag in activation of glucose transport



Coupling of insulin receptors to glucose transport a temperature dependent time lag in activation of glucose transport



Archives of Biochemistry & Biophysics 193(1): 221-231



The ability of occupied insulin receptors to activate (or couple to) the glucose transport system was studied in isolated rat adipocytes. Maximal insulin action was seen when only a small proportion (< 10%) of the receptors was occupied and this fraction can be rapidly filled (< 5 s) at an insulin concentration of 100 ng/ml. Additionally, control studies showed that when the extracellular glucose concentration was tripled, the rate of transport tripled within 10 s, indicating that changes in transport activity can be observed nearly instantaneously. When cells are exposed to a high insulin concentration (100 ng/ml), any delay in the onset of insulin action beyond this time must be due to the time required for coupling of occupied insulin receptors to the glucose transport system. At 24.degree. C there was a lag of at least 200 s after insulin addition before a significant stimulation of 2-deoxyglucose transport was seen. The length of this lag phase was temperature dependent, decreasing to 45 s at 37.degree. C. An Arrhenius plot of the coupling lag was linear, with an activation energy of 25 kcal/mol. After the delay in the onset of initial transport activation the full response appears in a gradual manner, requiring 20 min at 24.degree. C to attain maximal stimulation. The time required for the full insulin response to appear was also temperature dependent, decreasing to 5 min at 37.degree. C. Similar results were obtained for the kinetics of insulin activation of 3-O-methyl glucose transport. The coupling of insulin receptors to the glucose transport system can be divided into 2 components: an initial absolute time lag followed by a gradual incremental process before the maximal, or full, effect of insulin is achieved. There is an absolute delay in the onset of the insulin's initial action on glucose transport; after an initial delay, activation of transport proceeds in a gradual manner; the coupling process between insulin receptors and the glucose transport system is temperature dependent and can be described by a linear Arrhenius plot. The rate of activation is apparently not limited by membrane fluidity.

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Accession: 005065304

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PMID: 453850


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