The role of insulin, insulin-like growth factor-I and growth hormone in counteracting dexamethasone induced nitrogen wasting in rats.

Administration of glucocorticoids is associated with decreased nitrogen balance. The main aim of the present study was to elucidate whether this could be counteracted by subcutaneous infusions of rhGH (360 micrograms/d), rhIGF-1 (500 micrograms/d) or insulin (39 micrograms/d). During a study period of 8 days one out of 10 groups of rats received dexamethasone (dex, 26 micrograms/d) alone, whereas 7 groups were given one or more of the three peptides in combination with dex. One group was given saline alone and one was food restricted to match the average food intake among dex groups. Food restriction and saline alone produced relative nitrogen balances, retained N/ingested N (x100) of 44 (SE 3) and 36% (SE 4), respectively. This was decreased (p < 0.001) to 7% (SE 3) with dex alone. However, if either insulin/rhGH/rhIGF-1, rhIGF-1 alone or insulin/rhIGF-1 were given together with dex, the relative nitrogen balances increased significantly (p < 0.03) up to 16, 22 and 24% (SE 3), respectively. Insulin or rhGH alone were without effect as was rhGH combined with either rhIGF-I or insulin. Although the relative nitrogen balances associated with insulin/rhIGF-1 and rhIGF-1 alone were not found to be significantly different, the former infusion regimen produced a significantly (p < 0.02) lower plasma urea. It is concluded that in the rat, rhIGF-1 has a potential to counteract the decrease in nitrogen balance induced by potent glucocorticoids, whereas rhGH as administered in this experiment does not have this effect.

Effects of insulin-like growth factor I (IGF-I) on the small intestine: a comparison between oral and subcutaneous administration in the weaned rat.

Several studies have suggested that growth factors play an important role in the development and the maintenance of the gastrointestinal tract. Colostrum and normal breast milk as well as intestinal secretion are reported to contain IGF-I. Thus, the objective of this study was to investigate whether the route of administration of IGF-I, subcutaneously and orally, was important for the way of influencing the gastrointestinal tract in the weaned rat and further to observe if this effect was affected by different feed regimens. Well nourished weaned rats subcutaneously administered IGF-I (2 mg/kg body weight and day during 14 days) were found to have significantly increased relative weights of the small intestine, increased duodenal crypt depths and villi heights compared with control rats. The same dose given orally in bovine milk had no effect. Furthermore, a study was performed with the same dose of IGF-I given for 7 days together with a restricted feed regimen. Similar observations, although of a slightly smaller magnitude, were found. These observations indicate that the effect of IGF-I on gastrointestinal renewal in the weaned rat is not depending on an IGF-I supply through the gastrointestinal fluids but rather through a supply via the circulation or by a local intestinal production. The effects were statistically significant both in well fed and malnourished conditions.

Effects of insulin-like growth factor-I and growth hormone on the net flux of amino acids across the hind limbs in the surgically traumatized pig.

1. After surgery three groups of six female pigs weighing on average 52.2 kg (SD 3.5) received vehicle, recombinant insulin-like factor-1 (364.4 micrograms day-1 kg-1) or recombinant human growth hormone (467.7 m-i.u. day-1 kg-1) for two post-operative days. Vehicle and peptides were infused intravenously together with total parenteral nutrition providing 129 kJ day-1 kg-1 non-protein calories and 0.35 g N day-1 kg-1. 2. On both post-operative days the mean concentration of insulin-like growth factor-1 in arterial blood samples was clearly below presurgical levels in animals receiving vehicle or recombinant human growth hormone, whereas recombinant human insulin-like growth factor-1 infusions more than restored insulin-like growth factor-1 concentrations. These last samples, however, contained significantly (P < 0.05) less insulin than those from other animals. 3. Infusion of recombinant human growth factor was often associated with higher circulating levels of amino acids compared with recombinant human insulin-like growth factor-1 infusions. Despite this, both hormones significantly (P < 0.05) increased the hind limb net balance of total amino acids on post-operative day 1. Net balances of -44.2, +69.5 and +100.9 mumol/min (pooled SE 35.3) were associated with infusion of vehicle, recombinant human insulin-like growth factor-1 and recombinant human growth hormone respectively. This response was also closely reflected in the group of non-essential amino acids. 4. The net efflux of alanine from the hind limbs was also significantly (P < 0.002) reduced, whereas glutamine was less affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic and tissue repair functions of recombinant insulin-like growth factor I.

Recombinant human insulin-like growth factor I (rhIGF-I) has been produced in yeast and purified using conventional biochemical techniques. It has been shown to have receptor-binding properties and in vitro growth-promoting activities comparable to those of plasma-derived IGF-I. The anabolic actions of IGF-I can be studied using both systemic and local administration in vivo. The growth-promoting activity and systemic anabolic actions of recombinant IGF-I were studied in mutant dwarf rats. IGF-I was infused intravenously for 9 days and resulted in a significant gain in body weight and significant bone growth, though the effects were not as great as those observed with human growth hormone (hGH). IGF-I also had selective effects on specific organs which were not observed in hGH-treated animals. The results indicate that the growth-promoting effects of IGF-I show a different pattern compared to hGH. The effects of local administration of recombinant IGF-I on tissue regeneration and maintenance were also studied in hypophysectomized and normal rats. After hypophysectomy, the regeneration processes were impaired when both peripheral nerve regeneration and incision wound healing were considered. The results indicate that local administration could have significant effects on regeneration of, for example, peripheral nerves.

Effects of human growth hormone on peripheral nerve regeneration.

Systemic administration of human growth hormone (hGH) to intact or hypophysectomized rats was found to stimulate regeneration of the crush-lesioned sciatic nerve. The IGF-I levels of serum of the treated rats did not correlate with regeneration of the nerve but hGH treatment increased the IGF-I content of the nerve. The results suggest that a GH-mediated increase of IGF-I in the sciatic nerve could be involved in the stimulatory effect of GH on neurite outgrowth.