A comparison of changes in whole body and skin amino acid metabolism of sheep in response to 24 h continuous infusions of variants of insulin-like growth factor 1

Abstract

Because of the economic significance of wool to many sheep production systems, attempts to partition amino acids towards skin and wool protein synthesis have included both nutritional and hormonal methods of manipulation. A variant of insulin-like growth factor 1 (IGF-1) has previously been shown to transiently increase protein synthesis in the skin of sheep and the current study extended that work by comparing the effects of a 24 h, close-arterial, skin infusion of IGF-1, in the form of either recombinant human (rhIGF-1) or an extended variant (LR3IGF-1), on both whole body and skin amino acid metabolism adult, castrated Romney sheep, with three animals allocated to each treatment. There were no differences in food intake between the two treatment groups. The plasma concentration of immunoreactive IGF-1 of sheep infused with rhIGF-1 increased (P < 0.01) with time of administration, but decreased (P < 0.05) after 24 h of LR3IGF-1 infusion. Administration of both IGF-1 variants caused a substantial and sustained decrease in arterial insulin to less than 50% (P < 0.05) of pre-infusion values, while arterial plasma glucose concentrations were only reduced by 7%. Alterations in whole body and skin protein metabolism were assessed from continuous infusions of mixed [U-13C] AA, [2,6 ring 3H]phenylalanine and [35S]cysteine. Within 4 h both AA concentrations and whole body plasma ILR of essential and non-essential AA were decreased (P < 0.05 for seven AA) by IGF-1 infusions. Both IGF1 variants caused acute increases (P < 0.05) in skin blood flow and, for 13 of the 15 AA measured, isotopic transfers (range 50–220%; P < 0.05 for cysteine and tyrosine), which probably reflect increased protein synthesis. By 24 h skin blood flow, AA uptake and protein synthesis had returned to pre-infusion values. Strategies based on exogenous application, or enhanced endogenous production, of IGF-1 are unlikely, therefore, to produce persistent anabolic responses. Key words: Insulin-like growth factor 1, skin, sheep, protein synthesis