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J. Biol. Chem., Vol. 263, Issue 30, 15386-15391, 10, 1988
P Lonnroth, KC Appell, C Wesslau, SW Cushman, IA Simpson and U Smith
Insulin shifts the steady-state subcellular distribution of insulin- like
growth factor II (IGF-II) receptors from a large intracellular pool to the
plasma membrane in the rat adipose cell (Wardzala, L. J., Simpson, I. A.,
Rechler, M. M., and Cushman, S. W. (1984) J. Biol. Chem. 259, 8378-8383).
In the present study, the counterregulatory effects of adrenergic
stimulation, adenosine deaminase, and cAMP on this process were studied.
Both isoproterenol (10(-6) M) and adenosine deaminase reduced insulin
sensitivity and also rapidly (t1/2 approximately 1.5 min) decreased the
effect of a maximal insulin concentration on the number of cell surface
IGF-II receptors by 35-50%, and by 70% when added together. The marked
reduction in binding was retained in isolated and solubilized plasma
membranes. Both isoproterenol and adenosine deaminase alone increased the
EC50 for insulin from 0.06 to 0.17 nM and, when combined, to 0.6 nM. N6-
Monobutyryl-cAMP and 8-bromo-cAMP were equally potent in reducing IGF- II
binding in the absence of insulin and inhibited maximal insulin- stimulated
IGF-II binding by 60 and 30%, respectively. However, only the
nonhydrolyzable cAMP analogue, N6-monobutyryl-cAMP, reduced the insulin
sensitivity (EC50 0.7 nM). An important stimulatory role for Gi (guanine
nucleotide-binding regulatory protein that inhibits adenylate cyclase) was
indicated by the altered activities of cells from pertussis toxin-treated
animals. The results suggest that beta- adrenergic stimulation through a
cAMP-dependent mechanism markedly alters the insulin-stimulated
redistribution of IGF-II receptors. This effect is additional to the potent
antagonistic action of cAMP on insulin's signalling mechanism.
Insulin-induced subcellular redistribution of insulin-like growth factor II receptors in the rat adipose cell. Counterregulatory effects of isoproterenol, adenosine, and cAMP analogues
Department of Medicine II, Sahlgren's Hospital, Gothenburg, Sweden.
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