Integral membrane protein translocations in the mechanism of insulin action

S. W. Cushman, I. A. Simpson

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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.

Original languageEnglish (US)
Pages (from-to)127-149
Number of pages23
JournalBiochemical Society Symposia
VolumeNO. 50
StatePublished - 1985

All Science Journal Classification (ASJC) codes

  • Biochemistry


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