Parenteral amino acid intake alters the anabolic actions of insulin-like growth factor I in rats

Abstract

The anabolic properties of insulin-like growth factor (IGF) I are attenuated by oral diets that are low in protein. However, it is not known whether parenteral nutrition (PN) providing a low amino acid (AA) input will influence IGF-I action. With the use of a rat model, this study examined the interaction between AA input (1.27 and 0.62 g N ⋅ kg body wt−1 ⋅ 24 h−1, AA and ½AA groups, respectively) and recombinant human IGF-I (rhIGF-I, 2.5 mg ⋅ kg body wt−1 ⋅ 24 h−1) infusion on the composition of the carcass and organs and on plasma insulin, IGF-I, IGF-binding protein 1 (IGFBP-1), and acid-labile subunit (ALS) concentrations. Carcass protein deposition only occurred in the AA groups ( P < 0.003) and was not influenced by administration of rhIGF-I. However, visceral protein loss persisted in the AA group but was prevented by rhIGF-I infusion. The changes in water content of the carcass and the organs were generally in the expected proportion of normal lean tissue. The accumulation of lipid that follows the infusion of the AA-deficient PN was prevented by rhIGF-I infusion, which may indicate an improved energy utilization. Neither serum insulin nor ALS concentrations were influenced by the level of AA infusion but were reduced by rhIGF-I administration. However, plasma IGF-I levels were elevated by higher AA infusion and by IGF-I administration. Also, IGFBP-1 concentrations were reduced by the higher AA infusion and increased with rhIGF-I administration. Interestingly, there was a significant interaction effect between both of these influences. It is concluded that free IGF-I concentration, which may be regulated by IGFBP-1 through a direct effect of AAs on the liver, may have an important role in regulating anabolism in visceral and possibly skeletal tissue during PN.

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“…Furthermore, the free glucose lowering fraction of IGF-1 depends on changes in IGFBP-1, the only binding protein demonstrated to have acute metabolic effects [50]. In the amino acid-treated rats, a higher concentration of total IGF-1 was detected [48] in agreement with our findings. Our results suggest that preoperative amino acid infusion has a pharmacological effect and preserves IGFBP-1 postoperatively in traumatized individuals.…”

“…The most probable reason for this is the different regimes of amino acid administration. An infusion of amino acids in rats caused a decrease in IGFBP-1 without any changes in insulin [48]. A decrease in IGFBP-1 with unchanged insulin levels is known to reflect an improved hepatic insulin sensitivity [49].…”

Regulation of Insulin-Like Growth Factor-I by Nutrition

“…Similarly, IGF-I failed to increase cancellous and periosteal bone formation in protein-restricted rats, while exogenous IGF-I increased the bone formation rate in well-fed rats (203). In rats fed parenterally with a limited supply of amino acids, anabolic effects of IGF-I on carcass lean mass were not observed, in contrast to visceral tissues (204). Treatment of neonatal protein energydeprived rats with IGF-I does not stimulate somatic growth.…”

IGF-I treatment facilitates transition from parenteral to enteral nutrition in rats with short bowel syndrome

“…As mentioned above, several studies found no effect on body composition in parenterally fed rats given similar amounts of IGF-I (11,26). These authors suggest that this finding may be related to a lack of stress in their studies and/or the use of young animals already growing maximally.…”