The insulin-like effect of growth hormone on insulin-like growth factor II receptors is opposed by cyclic AMP. Evidence for a common post-receptor pathway for growth hormone and insulin action.
The counter-regulatory effects of beta-adrenergic stimulation and cyclic AMP on the insulin-like action of growth hormone (GH) on the subcellular distribution of insulin-like growth factor II (IGF-II) receptors were studied in fat cells from hypophysectomized (Hx) and sham-operated rats. For comparison, the effect of insulin on this process was also studied. Basal IGF-II binding was increased by approx. 2-fold in cells from Hx as compared with sham-operated animals. The stimulatory effect of insulin was decreased in Hx cells, mainly due to a basal redistribution but also to a reduced total number of receptors. GH exerted an acute insulin-like effect in cells from Hx rats and stimulated the translocation of IGF-II receptors from an intracellular pool to the plasma membrane. beta-Adrenergic stimulation with isoprenaline or addition of the non-metabolizable cyclic AMP-analogue N6-monobutyryl cyclic AMP induced a cellular resistance to both GH and insulin and also reduced the responsiveness to these hormones. Adenosine exerted a modulatory effect on both hormones. Binding of 125I-labelled GH to its receptors was not significantly changed by any of these factors. It is concluded that: (1) beta-adrenergic stimulation and cyclic AMP induce a cellular GH resistance at a level distal to the GH-binding site, and (2) the insulin-like effect of GH shares a common pathway with insulin which occurs at the post-binding level.
Eriksson
J
J
Department of Medicine II, Sahlgren's Hospital, University of Gothenburg, Sweden.
Gause-Nilsson
I
I
Lönnroth
P
P
Smith
U
U
D000241:Adenosine / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004347:Drug Interactions; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017451:Receptors, Somatomedin; D012995:Solubility; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; C002373:monobutyryl cyclic AMP; D003994:Bucladesine; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol