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

Abstract

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.

Cellular mechanism of the insulin-like effect of growth hormone in adipocytes. Rapid translocation of the HepG2-type and adipocyte/muscle glucose transporters

“…The insulin-like effect of GH in adipocytes is not limited, however, to increases in glucose uptake. It has recently been demonstrated that GH, like insulin, increases IGF-II binding to adipocyte membranes from hypophysectomized rats [53].…”

Insulin Can Rapidly Increase Cell Surface Insulin Binding Capacity in Rat Adipocytes: A Novel Mechanism Related to Insulin Sensitivity

“…To achieve this, the cells were energy depleted with KCN after the preincubation period, thus preventing receptor internalization (26)(27)(28) and allowing assessment of the ambient surface binding capacity. This approach has been successfully used to characterize the effect of insulin and growth hormone on insulinlike growth factor II receptors in rat adipocytes (29)(30)(31). It also has been used to assess cell surface insulin binding to fat cells both in a study by Fantus et al (32), in which the insulin-mimicking agent vanadate was shown to increase insulin binding (32) and also in a study in which we investigated the interaction between amiloride and insulin action (33).…”