Effects of Insulin and Postruminal Supply of Protein on Use of Amino Acids by the Mammary Gland for Milk Protein Synthesis

Mackle, T.R.; Dwyer, D.A.; Ingvartsen, Klaus Lønne; Chouinard, P.Y.; Ross, Deborah; Bauman, Dale E.

doi:10.3168/jds.s0022-0302(00)74860-0

Cited by 121 publications

(128 citation statements)

References 40 publications

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“…Thus, mammary blood flow is apparently also subjected to other systemic control mechanisms and is affected by milk yield (Lescoat et al, 1996) and long-term administration of recombinant bovine somatropin, which increases mammary blood flow by 20% to 30% (Chaiyabutr et al, 2005). Mackle et al (2000) and Bequette et al (2001) observed a 40% and 50% increase in mammary blood flow during a 4-day hyperinsulinemic-euglycemic clamp in dairy cows and goats, respectively. The effect of these hormones on blood supply of AA is most likely an orchestrated mechanism consistent with the high protein production in early lactation.…”

Section: Factors Affecting the Efficiency Of N Utilization In The Mammentioning

confidence: 96%

Strategies for optimizing nitrogen use by ruminants

Calsamiglia

Ferret

Reynolds

et al. 2010

Animal

260

165

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The efficiency of N utilization in ruminants is typically low (around 25%) and highly variable (10% to 40%) compared with the higher efficiency of other production animals. The low efficiency has implications for the production performance and environment. Many efforts have been devoted to improving the efficiency of N utilization in ruminants, and while major improvements in our understanding of N requirements and metabolism have been achieved, the overall efficiency remains low. In general, maximal efficiency of N utilization will only occur at the expense of some losses in production performance. However, optimal production and N utilization may be achieved through the understanding of the key mechanisms involved in the control of N metabolism. Key factors in the rumen include the efficiency of N capture in the rumen (grams of bacterial N per grams of rumen available N) and the modification of protein degradation. Traditionally, protein degradation has been modulated by modifying the feed (physical and chemical treatments). Modifying the rumen microflora involved in peptide degradation and amino acid deamination offers an alternative approach that needs to be addressed. Current evidence indicates that in typical feeding conditions there is limited net recycling of N into the rumen (blood urea-N uptake minus ammonia-N absorption), but understanding the factors controlling urea transport across the rumen wall may reverse the balance to take advantage of the recycling capabilities of ruminants. Finally, there is considerable metabolism of amino acids (AA) in the portal-drained viscera (PDV) and liver. However, most of this process occurs through the uptake of AA from the arterial blood and not during the 'absorptive' process. Therefore, AA are available to the peripheral circulation and to the mammary gland before being used by PDV and the liver. In these conditions, the mammary gland plays a key role in determining the efficiency of N utilization because the PDV and liver will use AA in excess of those required by the mammary gland. Protein synthesis in the mammary gland appears to be tightly regulated by local and systemic signals. The understanding of factors regulating AA supply and absorption in the mammary gland, and the synthesis of milk protein should allow the formulation of diets that increase total AA uptake by the mammary gland and thus reduce AA utilization by PDV and the liver. A better understanding of these key processes should allow the development of strategies to improve the efficiency of N utilization in ruminants. Keywords: ruminant, nitrogen efficiency ImplicationsRuminants have a low efficiency of N utilization compared with non-ruminants. This low efficiency has implications not only for production performance and economic efficiency but also for the emission of contaminants to the environment. The efficiency of N utilization can be improved through the understanding and modification of factors regulating the efficiency of N utilization in key processes, including N capture in the rumen, ...

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Section: Factors Affecting the Efficiency Of N Utilization In The Mammentioning

confidence: 96%

Strategies for optimizing nitrogen use by ruminants

Calsamiglia

Ferret

Reynolds

et al. 2010

Animal

260

165

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“…4b). The implication that restoration of ATP balance was again responsible for the hemodynamic response is supported by the observation that abomasal casein infusion during hyperinsulinemia did not influence MBF (Mackle et al 2000a). Were the hyperemia an attempt to provide AA for protein synthesis, then the casein infusion should have lessened the demand.…”

Section: Mammary Blood Flowmentioning

confidence: 98%

“…Two different groups have reported that euglycemic insulin infusion into lactating ruminants increases both MBF and milk protein yield (Mackle et al 2000a;Bequette et al 2001), the former ostensibly to provide AA for the latter. Mackle et al (2000a) infused cows abomasally with water or casein, each with or without euglycemic insulin infusion for 4 d. Neither acetate nor β-hydroxybutyrate concentrations in plasma were reported but a decline in both would be expected.…”

Section: Mammary Blood Flowmentioning

confidence: 99%

“…Mackle et al (2000a) infused cows abomasally with water or casein, each with or without euglycemic insulin infusion for 4 d. Neither acetate nor β-hydroxybutyrate concentrations in plasma were reported but a decline in both would be expected. Increasing plasma insulin concentration sixfold in sheep resulted in a 60% drop in 2C concentration (Brockman and Laarveld 1985).…”

Section: Mammary Blood Flowmentioning

confidence: 99%

“…4b) but neither was the increased extraction of essential AA from plasma (Mackle et al 2000a;Bequette et al 2001) which would have increased predicted protein yields, ATP utilization and MBF. The mechanism by which insulin stimulates milk protein secretion is unknown (Mackle et al 2000b) and so it is premature to model putative effects on AA transport for this discussion.…”

Section: Mammary Blood Flowmentioning

confidence: 99%

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Responses of the bovine mammary glands to absorptive supply of single amino acids

Cant¹,

Berthiaume²,

Lapierre³

et al. 2003

Can. J. Anim. Sci.

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Responses of the bovine mammary glands to absorptive supply of single amino acids. Can. J. Anim. Sci. 83: [341][342][343][344][345][346][347][348][349][350][351][352][353][354][355]. In this review, we discuss the mechanisms of responses of various tissues of the lactating dairy cow, particularly the mammary glands, to perturbations in supply of single amino acids that result in observed milk protein yields. Additions of methionine, lysine, histidine or leucine to the absorptive supply cause arterial concentrations of these amino acids to increase, mammary extractions to drop and mammary blood flow to decrease. Single subtractions of essential amino acids have the opposite effect. Changes in mammary blood flow that have been recorded can be explained as attempts by the mammary glands to restore intracellular ATP balance in the face of altered concentrations of energy metabolites in the general circulation. In a quantitative sense, milk protein yield is relatively insensitive to fluctuations in arterial amino acid concentrations but can be stimulated by any one of a number of amino acids. In this context, it is suggested that the designation of a limiting amino acid is not appropriate to the purpose of predicting milk protein yield. Rather, milk protein synthesis appears to operate at a predetermined rate set by external communications of milk withdrawal rate, physiological state and overall nutritional status. Utilization of amino acids (AA) by splanchnic and peripheral tissues, in coordination with the mammary setpoint, offsets imperfections in the dietary AA supply. How strongly an individual AA influences the mammary setpoint, arterial concentrations of energy metabolites, and mammary AA transport capacity will determine the magnitude of the milk protein yield response when its absorptive supply is changed. Dans cet article, les auteurs examinent comment certains tissus de la vache laitière en lactation, principalement la glande mammaire, réagissent à une modification de l'apport de certains acides aminés entraînant un changement du rendement du lait en protéines. L'addition de méthionine, de lysine, d'histidine ou de leucine aux acides aminés absorbés augmente leur concentration dans le sang artériel et la diminue dans les sécrétions et le sang de la glande mammaire. La soustraction d'un de ces acides aminés a l'effet contraire. On explique les variations observées au niveau de la circulation sanguine dans la glande mammaire par les efforts que cette dernière déploie pour rétablir l'équilibre de l'ATP après modification de la quantité de métabolites porteurs d'énergie dans la circulation générale. Sur le plan quantitatif, le rendement du lait en protéines est relativement insensible aux fluctuations de la concentration d'acides aminés dans le sang artériel, mais il est stimulé par plusieurs acides aminés. On estime qu'il est impossible de prévoir le rendement du lait en protéines à partir d'un acide aminé limitant. En effet, les protéines laitières semblent être synthétisées à un taux préétabli par les rappo...

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Negative effects of the amino acids Lys, His, and Thr on S6K1 phosphorylation in mammary epithelial cells

Prizant

Barash

2008

J of Cellular Biochemistry

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The role of essential amino acids (AA) on protein synthesis via the mTOR pathway was studied in murine mammary epithelial cells cultured under lactogenic conditions. Leu, Ile, and Val increased S6K1 phosphorylation compared to that measured in AA-deprived cells. Trp, Phe, and Met had no effect. Surprisingly, Lys, His, and Thr inhibited S6K1 phosphorylation in both murine and bovine mammary cells. Thr exhibited the most potent inhibition, being the only amino acid that competed with Leu's positive role. In non-deprived cells, there was no observable effect of Lys, His, or Thr on S6K1 phosphorylation at concentrations up to five times those in the medium. However, their addition as a mix revealed a synergistic negative effect. Supplementation of Lys, His, and Thr abrogated mTOR Ser 2448 phosphorylation, with no effect on Akt Ser 473-an mTORC2 target. This confirms specific mTORC1 regulation of S6K1 phosphorylation. The individual supplementation of Lys, His, and Thr maintained a low level of IRS-1 phosphorylation, which was dose-dependently increased by their combined addition. Thus, in parallel to inhibiting S6K1 activity, these AA may act synergistically to activate an additional kinase, phosphorylating IRS-1 via an S6K1-independent pathway. In cultures supplemented by Lys, His, and Thr, cellular protein synthesis decreased by up to 65%. A more pronounced effect was observed on beta-casein synthesis. These findings indicate that positive and negative signaling from AA to the mTOR pathway, combined with modulation of insulin sensitization, mediate the synthesis rates of total and specific milk proteins in mammary epithelial cells.

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Effects of Insulin and Postruminal Supply of Protein on Use of Amino Acids by the Mammary Gland for Milk Protein Synthesis

Cited by 121 publications

References 40 publications

Strategies for optimizing nitrogen use by ruminants

Strategies for optimizing nitrogen use by ruminants

Responses of the bovine mammary glands to absorptive supply of single amino acids

Negative effects of the amino acids Lys, His, and Thr on S6K1 phosphorylation in mammary epithelial cells

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