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Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs

  • T. J. Wester (a1), G. E. Lobley (a2), L. M. Birnie (a1), L. A. Crompton (a3), S. Brown (a2), V. Buchan (a2), A. G. Calder (a2), E. Milne (a3) and M. A. Lomax (a4)...

The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0·778 μmol leucine, 0·640 μmol isoleucine and 0·693 μmol valine/min·kg); (3) 18·7 μmol glucose/min·kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine (Phe) as follows: (1) l-[1-13C]Phe; (2) l-phenyl-[ring 2H5]-alanine; (3) l-[15N]Phe; (4) l-[ring 2,6-3H]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, Ks was increased by an average of 40 % at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on Ks compared with control sheep. Ks was approximately 60 % greater for vastus muscle than for m. longissimus dorsi (P>0·01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in Ks in muscle of growing ruminant animals.

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      Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs
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Baillie AG & Garlick PJ Responses of protein synthesis in different skeletal muscles to fasting and insulin in rats. Am J Physiol (1991) 260, E891E896.
Baillie AG & Garlick PJ Attenuated responses of muscle protein synthesis to fasting and insulin in adult female rats. Am J Physiol (1992) 262, E1E5.
Barua JM, Wilso E, Downie S, Weryk B, Cuschieri A & Rennie MJ The effect of alanyl glutamine peptide supplementation on muscle protein synthesis in post-surgical patients receiving glutamine-free amino acids intravenously. Proc Nutr Soc (1992) 51, 115A.
Bennet WM, Connacher AA, Scrimgeour CM, Jung RT & Rennie MJ Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia. Am J Physiol (1990) 259, E185E194.
Bequette BJ, Kyle CE, Crompton LA, Anderson SE & Hanigan MD Protein metabolism in lactating goats subjected to the insulin clamp. J Dairy Sci (2002) 85, 15461555.
Biolo G, Declan Fleming RY & Wolfe RR Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest (1995) 95, 811819.
Calder AG, Anderson SE, Grant I, McNurlan MA & Garlick PJ The determination of low phenylalanine enrichment (0·002–0·09 atom percent excess) after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography (electron ionisation) mass spectrometry. Rapid Commun Mass Spectrom (1992) 6, 421424.
Calder AG & Smith A Stable isotope ratio analysis of leucine and ketoisocaproic acid in blood plasma by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom (1988) 2, 1416.
Cole NA, Purdy CW & Hallford DM Influence of fasting and postfast diet energy level on feed intake, feeding pattern and blood variables of lambs. J Anim Sci (1988) 66, 798805.
Crompton LA & Lomax MA The relationship between hindlimb muscle protein metabolism and growth hormone, insulin, cortisol and thyroxine in growing lambs. Proc Nutr Soc (1987) 46, 45A.
Crompton LA & Lomax MA (1993) Hindlimb protein turnover and muscle protein synthesis in lambs: a comparison of techniques. Br J Nutr 69, 345348.
Davis TA, Fiorotto ML, Beckett PR, Burrin DG, Reeds PJ, Wray-Cahen D & Nguyen HV Differential effects of insulin on peripheral and visceral tissue protein synthesis in neonatal pigs. Am J Physiol (2001) 280, E770E779.
Dawson JM, Buttery PJ, Lammiman MJ, Soar JB & Essex CP Nutritional and endocrinological manipulation of lean deposition in forage-fed steers. Br J Nutr (1991) 66, 171185.
Douglas RG, Gluckman PD, Ball K, Breier B & Shaw JH The effects of infusion of insulin-like growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs. J Clin Invest (1991) 88, 614622.
Ferrando AA, Williams BD, Stuart CA, Lane HW & Wolfe RR Oral branched-chain amino acids decrease whole-body proteolysis. J Parenter Enteral Nutr (1995) 19, 4754.
Fryburg DA, Barret EJ, Louard RJ & Gelfand RA Effect of starvation on human muscle protein metabolism and its response to insulin. Am J Physiol (1990) 259, E477E482.
Fryburg DA, Jahn LA, Hill SA, Oliveras DM & Barrett EJ Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by differential mechanisms. J Clin Invest (1995) 96, 17221729.
Garlick PJ, Fern M & Preedy VR The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats. Biochem J (1983) 210, 669676.
Garlick PJ & Grant I Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin: effect of branched-chain amino acids. Biochem J (1988) 254, 579584.
Garlick PJ, McNurlan MA, Bark T, Lang CH & Gelato MC Hormonal regulation of protein metabolism in relation to nutrition and disease. J Nutr (1998) 128, 356S359S.
Garlick PJ, Maltin CA, Baillie AGS, Delday MI & Grubb DA Fiber-type composition of nine rat muscles. II Relationship to protein turnover. Am J Physiol (1989) 257, E828E832.
Heinrikson RL & Meredith SC Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal Biochem (1984) 136, 6574.
Heitmann RN & Bergman EN Integration of amino acid metabolism in sheep: effects of fasting and acidosis. Am J Physiol (1980) 239, E248E254.
Hillier TA, Fryburg DA, Jahn LA & Barrett EJ Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm. Am J Physiol (1998) 274, E1067E1074.
Hoskin SO, Savary IC, Zuur G & Lobley GE Effect of feed intake on ovine hindlimb protein metabolism based on thirteen amino acids and arterio–venous techniques. Br J Nutr (2001) 86, 577585.
Hoskin SO, Savary-Auzeloux IC, Calder AG, Zuur G & Lobley GE Effect of feed intake on amino acid transfers across ovine hindquarters. Br J Nutr (2003) 89, 167179.
Jepson MM, Bates PC & Millward DJ The role of insulin and thyroid hormones in the regulation of muscle growth and protein turnover in response to dietary protein in the rat. Br J Nutr (1988) 59, 397415.
Kriel GV, Bryant MJ & Lomax MA Effect of dietary protein intake and intravenous glucose infusion on plasma concentrations of insulin-like growth factor-I in lambs. J Endocrinol (1992) 132, 195199.
Larbaud D, Debras E, Taillandier D, Samuels SE, Temparis S, Champredon C, Grizard J & Attaix D Euglycemic hyperinsulinemia and hyperaminoacidemia decrease skeletal muscle ubiquitin mRNA in goats. Am J Physiol (1996) 271, E505E512.
Lobley GE, Bremner DM, Nieto R, Obitsu T, Hotson Moore A & Brown DS Transfers of N metabolites across the ovine liver in response to short-term infusions of an amino acid mixture into the mesenteric vein. Br J Nutr (1998) 80, 371379.
Lobley GE, Connell A, Milne E, Buchan V, Calder AG, Anderson SE & Vint H Muscle protein synthesis in response to testosterone administration in wether lambs. Br J Nutr (1990) 64, 691704.
Lobley GE, Harris PM, Skene PA, Brown D, Milne E, Calder AG, Anderson SE, Garlick PJ, Nevison I & Connell A Responses in tissue protein synthesis to sub- and supra-maintenance intake in young growing sheep: comparison of large-dose and continuous-infusion techniques. Br J Nutr (1992) 68, 373388.
Lobley GE, Sinclair KD, Grant CM, Miller L, Mantle D, Calder AG, Warkup CC & Maltin CA The effects of breed and level of nutrition on whole-body and muscle protein metabolism in pure-bred Aberdeen Angus and Charolais beef steers. Br J Nutr (2000) 84, 275284.
Lomax MA & Baird GD Blood flow and nutrient exchange across the liver and gut of the dairy cow. Effects of lactation and fasting. Br J Nutr (1983) 49, 481496.
McNurlan MA & Garlick PJ Protein metabolism in the cancer patient. Biochimie (1994) 76, 713717.
Maltin CA, Lobley CE, Grant CM, Miller LA, Kyle DJ, Horgan GW, Matthews KR & Sinclair KD Factors influencing beef eating quality – 2. Effects of nutritional regimen and genotype on muscle fibre characteristics. Anim Sci (2001) 72, 279287.
Midgley AR, Rebau RW & Niswender GD Radioimmunoassays employing double antibody techniques. Acta Endocrinol (1969) 142, 247254.
Millward DJ, Fereday A, Gibson NR & Pacy PJ Post-prandial protein metabolism. Baillieres Best Pract Res Clin Endocrinol Metab (1996) 10, 533549.
Nicholas GA, Lobley GE & Harris CI Use of the constant infusion technique for measuring rates of protein synthesis in the New Zealand White rabbit. Br J Nutr (1977) 38, 117.
Oddy VH, Lindsay DB, Barker PJ & Northrop AJ Effect of insulin on hindlimb and whole-body leucine and protein metabolism in fed and fasted sheep. Br J Nutr (1987) 58, 143154.
Papet I, Glomot F, Grizard J & Arnal M Leucine excess under conditions of low or compensated aminoacidemia does not change skeletal muscle and whole-body protein synthesis in suckling lambs during postprandial period. J Nutr (1992) 122, 23072315.
Preedy VR & Garlick PJ The response of muscle protein synthesis to nutrient intake in postabsorptive rats: the role of insulin and amino acids. Biosci Rep (1986) 6, 177183.
Reecy JM, Williams JE, Kerley MS, MacDonald RS, Thornton WH Jr & Davis JL The effect of postruminal amino acid flow on muscle cell proliferation and protein turnover. J Anim Sci (1996) 74, 21582169.
Sandstrom R, Svanberg E, Hyltander A, Haglind E, Ohlsson C, Zachrisson H, Berglund B, Lindholm E, Brevinge H & Lundholm K The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals. Eur J Clin Invest (1995) 25, 784792.
Schaefer AL, Davis SR & Hughson GA Estimation of tissue protein synthesis in sheep during sustained elevation of plasma leucine concentration by intravenous infusion. Br J Nutr (1986) 56, 281288.
Svanberg E, Möller-Loswick A-C, Matthews DE, Körner U, Andersson M & Lunholm K Effects of amino acids on synthesis and degradation of skeletal muscle proteins in humans. Am J Physiol (1996 a) 271, E718E724.
Svanberg E, Zachrisson H, Ohlsson C, Iresjö B-M & Lundholm KG Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding. Am J Physiol (1996 b) 270, E614E620.
Tauveron I, Larbaud D, Champredon C, Debras E, Tesseraud S, Bayle G, Bonnet Y, Thieblot P & Grizard J Effect of hyperinsulinemia and hyperaminoacidemia on muscle and liver protein synthesis in lactating goats. Am J Physiol (1994) 267, E877E885.
Tesseraud S, Grizard J, Debras E, Papet I, Bonnet Y, Bayle G & Champredon C Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability. Am J Physiol (1993) 265, E402E413.
Waalkes TP & Udenfriend S A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med (1957) 50, 733736.
Watt PW, Corbett ME & Rennie MJ Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability. Am J Physiol (1992 a) 263, E453E460.
Watt PW, Hundal HS, Downie S & Rennie MJ Glutamine increase protein synthesis in heart, skeletal muscle, liver and gut of dexamethasone-treated rats. Proc Nutr Soc (1992 b) 51, 106A
Wester TJ, Lobley GE, Birnie LM & Lomax MA Insulin stimulates phenylalanine uptake across the hind limb in fed lambs. J Nutr (2000) 130, 608611.
Wray-Cahen D, Metcalfe JA, Backwell FR, Bequette BJ, Brown DS, Sutton JD & Lobley GE Hepatic response to increased exogenous supply of plasma amino acids by infusion into the mesentereic vein of Holstein–Friesian cows in late gestation. Br J Nutr (1997) 78, 913930.
Wray-Cahen D, Nguyen HV, Burrin DG, Beckett PR, Fiorotto ML, Reeds PR, Wester TJ & Davis TA Response of skeletal muscle protein synthesis to insulin in suckling pigs decreases with development. Am J Physiol (1998) 275, E602E609.
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British Journal of Nutrition
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