Regulation of insulin-like growth factor II receptors by growth hormone and insulin in rat adipocytes.

Abstract

The acute and long-term effects of growth hormone (GH) on the binding of insulin-like growth factor II (IGF-II) were evaluated in adipose cells from hypophysectomized rats given replacement therapy with thyroxine and hydrocortisone and in cells from their sham-operated littermates. After the cells were incubated with insulin and/or GH, the recycling ofIGF-ll receptors was metabolically inhibited by treating the cells with KCN. IGF-ll binding was 100 ± 20% higher in cells from GH-deficient animals when compared with sham-operated controls. These GH-deficient cells also showed an increased sensitivity for insulin as compared with control cells (the ECso for insulin was 0.06 ng/ml in GH-deficient cells and 0.3 ng/ml in control cells). However, the maximal incremental effect of insulin on IGF-H binding was reduced -27% by hypophysectomy. GH added to the incubation medium increased the number of IGF-ll binding sites by 100 ± 18% in cells from hypophysectomized animals. This increase was rapidly induced (til2, -10 min), but the time course was slower than that for the stimulatory effect of insulin. Half-maximal effect of GH on IGF-ll binding was obtained at =30 ng/ml.Thus, GH added in vitro exerted a rapid insulin-like effect on the number of IGF-ll receptors. GH also appears to play a regulating role for maintaining the cellular number of IGF-II receptors and, in addition, modulates the stimulatory effect of insulin on IGF-II binding.The insulin-like growth factors (IGF)-I and -II bind to specific receptors that mediate their growth-promoting effects (1, 2). The mechanisms for the growth-promoting effect of GH are still unclear. Recent data suggest that GH mediates cell differentiation, whereas the IGFs promote clonal expansion (3). Moreover, GH stimulates cellular production of IGF-I (4, 5).Both IGF-I and -II bind to insulin receptors and crossreact with each other's receptors with reduced affinity (1, 2, 6). A further interaction between these hormones is that the cellular binding of IGF-II to fat cells is increased following insulin exposure (2). Recently, the insulin-mediated increase of IGF-II binding to rat adipocytes was shown to be due to a recruitment of receptors from an intracellular pool to the plasma membrane (7). This effect markedly resembles the effect of insulin on the recruitment of glucose transport units (8, 9).Rat (10) and human (11) adipose cells possess specific cellular surface receptors for growth hormone (GH). GH produces insulin-like effects in these cells-such as enhancement of glucose metabolism and transport as well as inhibition of lipolysis (12)(13)(14).To elucidate whether GH exerts a regulatory effect on the cellular number of IGF-II receptors the effect of GH on IGF-II binding was studied in adipose cells from hypophysectomized rats and their sham-operated littermates. METHODSTissue Source. Male Sprague-Dawley rats, weighing 150-160 g, were hypophysectomized according to procedures described elsewhere (15). Each set of experiments was compared with data from sham-operated li...

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

“…Taken together, these observations indicate that GH exerts a chronic regulatory effect, which is opposite to its acute insulin-like effect, on the subcellular distribution of the IGF-Il receptors between the plasma membrane and the intracellular pool. This concept is supported by our findings that giving GH to Hx rats reduced the stimulatory effect of GH on IGF-II binding in vitro (Lonnroth et al, 1987a).…”

“…Under the experimental conditions currently employed, where the cells are energy-depleted after preincubation with GH or insulin, the increased IGF-II binding is due to a rapid redistribution of the binding sites from an intracellular pool to the plasma membrane rather than to changed affinity (Wardzala et al, 1984, Lonnroth et al, 1987a. The present data show that IGF-II binding to the total receptor pool from solubilized cells was unchanged whether or not the cells had been preincubated with GH or insulin.…”

“…We have shown previously that GH is also able to rapidly increase the number ofcell-surface IGF-II receptors in adipocytes from Hx rats without changing the receptor affinity (Lonnroth et al, 1987a). This effect of GH displayed may similarities with that of insulin, but clear differences were also found with respect to kinetics and magnitude.…”

Induction of interleukin‐1 receptors on chondrocytes by fibroblast growth factor: A possible mechanism for modulation of interleukin‐1 activity

“…Transmodulation of biological activity is a common feature among various growth factors. For example, PDGF increases the mitogenic response of cells to FGF, EGF, and IGF (Dicker et al, 1981;Olashaw et al, 1986;Lonnroth et al, 1987). Similarly, growth hormone increases the mitogenic response of cells to IGF, PDGF, and FGF (Pfeifle et al, 1987).…”

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).…”