TY - JOUR
T1 - Integral membrane protein translocations in the mechanism of insulin action
AU - Cushman, S. W.
AU - Simpson, I. A.
PY - 1985
Y1 - 1985
N2 - The subcellular distributions of insulin and insulin-like growth factor type II (IGF-II) receptors, and glucose transporters, have been examined, in basal and insulin-stimulated rat adipose cells. Plasma membranes (PM), high-density microsomes (HDM) and low-density microsomes (LDM) were prepared by differential ultracentrifugation. Insulin receptors were quantified by 125I-insulin binding or lactoperoxidase 125I-iodination and immunoprecipitation, IGF-II receptors by 125I-IGF-II binding, and glucose transporters by specific D-glucose-inhibitable [3H]cytochalasin B binding. In the basal state, more than 90% of the cells' insulin receptors are localized to PM, and ~ 90% of the cells' glucose transporters and IGF-II receptors are associated with LDM. In the maximally insulin-stimulated state, the number of insulin receptors in PM is decreased by ~ 30%, of which approximately half are recovered in LDM and the remainder in HDM in an inverted configuration. Concomitantly, the numbers of glucose transporters and IGF-II receptors in LDM are decreased by ~ 60% and ~ 22%, respectively, with stoichiometric numbers appearing in PM. All three redistribution processes are rapid (t( 1/2 ) = 2-3 min), achieving new steady states in 5-10 min. The redistributions of glucose transporters and IGF-II receptors are half-maximal at ~ 0.1 nM-insulin, whereas insulin receptor redistribution correlates with receptor occupancy (α2(max) κ 3 nM). Thus, insulin stimulates the rapid and simultaneous subcellular translocations of its own receptors and, in the opposite direction, IGF-II receptors and glucose transporters.
AB - The subcellular distributions of insulin and insulin-like growth factor type II (IGF-II) receptors, and glucose transporters, have been examined, in basal and insulin-stimulated rat adipose cells. Plasma membranes (PM), high-density microsomes (HDM) and low-density microsomes (LDM) were prepared by differential ultracentrifugation. Insulin receptors were quantified by 125I-insulin binding or lactoperoxidase 125I-iodination and immunoprecipitation, IGF-II receptors by 125I-IGF-II binding, and glucose transporters by specific D-glucose-inhibitable [3H]cytochalasin B binding. In the basal state, more than 90% of the cells' insulin receptors are localized to PM, and ~ 90% of the cells' glucose transporters and IGF-II receptors are associated with LDM. In the maximally insulin-stimulated state, the number of insulin receptors in PM is decreased by ~ 30%, of which approximately half are recovered in LDM and the remainder in HDM in an inverted configuration. Concomitantly, the numbers of glucose transporters and IGF-II receptors in LDM are decreased by ~ 60% and ~ 22%, respectively, with stoichiometric numbers appearing in PM. All three redistribution processes are rapid (t( 1/2 ) = 2-3 min), achieving new steady states in 5-10 min. The redistributions of glucose transporters and IGF-II receptors are half-maximal at ~ 0.1 nM-insulin, whereas insulin receptor redistribution correlates with receptor occupancy (α2(max) κ 3 nM). Thus, insulin stimulates the rapid and simultaneous subcellular translocations of its own receptors and, in the opposite direction, IGF-II receptors and glucose transporters.
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M3 - Article
C2 - 3915867
AN - SCOPUS:0022266610
SN - 0067-8694
VL - NO. 50
SP - 127
EP - 149
JO - Biochemical Society Symposia
JF - Biochemical Society Symposia
ER -