Inter‐organ metabolism of amino acids in vivo

Abumrad, Naji N.; Williams, Phillip E.; Frexes‐Steed, Maria; Geer, Richard J.; Flakoll, Paul J.; Cersósimo, Eugênio; Brown, Laurel L.; Melki, Ibrahim; Bulus, Nada; Hourani, Hisham; Hubbard, Margaret; Ghishan, Fayez K.

doi:10.1002/dmr.5610050302

Cited by 68 publications

(32 citation statements)

References 90 publications

(4 reference statements)

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“…However, in the second half of the experiment a marked increase in GNG was observed which primarily related to increased AA (substrate) supply and glucagon-mediated upregulation of gluconeogenic enzymes [11,52]. Furthermore, insulin-and glucagon-stimulated (hepatic) AA uptake [11,53] could have not only contributed to the up-regulation of GNG but also to the lower plasma AA concentrations during AA-S compared to AA+S. However, the rise in EGP was obviously counterbalanced by an insulin-stimulated increase in Rd, which thereby served to maintain fasting plasma glucose concentrations.…”

Section: Discussionmentioning

confidence: 99%

Direct and indirect effects of amino acids on hepatic glucose metabolism in humans

et al. 2003

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Aim/hypothesis. The study was designed to examine the contribution of direct (substrate-mediated) and indirect (hormone-mediated) effects of amino acids on hepatic glucose metabolism in healthy men. Methods. The protocols were: (i) CON+S (n=7): control conditions with somatostatin to inhibit endogenous hormone release resulting in fasting plasma concentrations of amino acids, insulin (~28 pmol/l) and glucagon (~65 ng/l), (ii) AA+S (n=7): amino acid infusion-fasting insulinaemia-fasting glucagonaemia, (iii) GLUC+S (n=6): fasting amino acids-fasting insulinaemia-hyperglucagonaemia (~99 ng/l) and (iv) AA-S (n=5): amino acid infusion without somatostatin resulting in amino acid-induced hyperinsulinaemia (~61 pmol/l)-hyperglucagonaemia (~147 ng/l). Net glycogenolysis was calculated from liver glycogen concentrations using 13 C nuclear magnetic resonance spectroscopy. Total gluconeogenesis (GNG) was calculated by subtracting net glycogenolysis from endogenous glucose production (EGP) which was measured with [6,6-2 H 2 ]glucose. Net GNG was assessed with the 2 H 2 O method. Results. During AA+S and GLUC+S, plasma glucose increased by about 50% (p<0.01) due to a comparable rise in EGP. This was associated with a 53-% (p<0.05) and a 65% increase (p<0.01) of total and net GNG during AA+S, whereas net glycogenolysis rose by 70% (p<0.001) during GLUC+S. During AA-S, plasma glucose remained unchanged despite nearlydoubled (p<0.01) total GNG. Conclusion/interpretation. Conditions of postprandial amino acid elevation stimulate secretion of insulin and glucagon without affecting glycaemia despite markedly increased gluconeogenesis. Impaired insulin secretion unmasks the direct gluconeogenic effect of amino acids and increases plasma glucose. [Diabetologia (2003) 46:917-925]

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Section: Discussionmentioning

confidence: 99%

Direct and indirect effects of amino acids on hepatic glucose metabolism in humans

et al. 2003

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“…To the best of our knowledge, this response has not been reported previously. Although the role of insulin in the regulation of muscle protein metabolism remains the subject of much discussion, the complexity of insulin's action is readily apparent (1,20,49). The effects of age on insulin sensitivity and ␤-cell function are also controversial.…”

Section: Discussionmentioning

confidence: 99%

Amino acid ingestion improves muscle protein synthesis in the young and elderly

Paddon‐Jones

Sheffield‐Moore

Zhang

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

393

317

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We recently demonstrated that muscle protein synthesis was stimulated to a similar extent in young and elderly subjects during a 3-h amino acid infusion. We sought to determine if a more practical bolus oral ingestion would also produce a similar response in young (34 Ϯ 4 yr) and elderly (67 Ϯ 2 yr) individuals. Arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 mol/kg) constant infusion (0.05Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated before and after the bolus ingestion of 15 g of essential amino acids (EAA) in young (n ϭ 6) and elderly (n ϭ 7) subjects. After EAA ingestion, the rate of increase in femoral artery phenylalanine concentration was slower in elderly subjects but remained elevated for a longer period. EAA ingestion increased FSR in both age groups by ϳ0.04%/h (P Ͻ 0.05). However, muscle intracellular (IC) phenylalanine concentration remained significantly higher in elderly subjects at the completion of the study (young: 115.6 Ϯ 5.4 nmol/ml; elderly: 150.2 Ϯ 19.4 nmol/ml). Correction for the free phenylalanine retained in the muscle IC pool resulted in similar net phenylalanine uptake values in the young and elderly. EAA ingestion increased plasma insulin levels in young (6.1 Ϯ 1.2 to 21.3 Ϯ 3.1 IU/ml) but not in elderly subjects (3.0 Ϯ 0.6 to 4.3 Ϯ 0.4 IU/ml). Despite differences in the time course of plasma phenylalanine kinetics and a greater residual IC phenylalanine concentration, amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals.

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“…In the postabsorptive state, glutamine is released from skeletal muscle, thus supplying an important metabolic fuel to the rapidly dividing cells of the intestine and immune system. Glutamine and alanine together make up 80% of the total amino acids released from this tissue (7,42,43). Glutamine also plays a significant role in skeletal muscle not only as a substrate for protein synthesis but also an effective modulator of protein turnover.…”

Section: Figmentioning

confidence: 99%

Primary Structure, Genomic Organization, and Functional and Electrogenic Characteristics of Human System N 1, a Na+- and H+-coupled Glutamine Transporter

Fei¹,

Sugawara²,

Nakanishi³

et al. 2000

Journal of Biological Chemistry

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We have cloned the human Na ؉ -and H ؉ -coupled amino acid transport system N (hSN1) from HepG2 liver cells and investigated its functional characteristics. Human SN1 protein consists of 504 amino acids and shows high homology to rat SN1 and rat brain glutamine transporter (GlnT). When expressed in mammalian cells, the transport function of human SN1 could be demonstrated with glutamine as the substrate in the presence of LiCl (instead of NaCl) and cysteine. The transport activity was saturable, pH-sensitive, and specific for glutamine, histidine, asparagine, and alanine. Analysis of Li ؉ activation kinetics showed a Li ؉ :glutamine stoichiometry of 2:1. When expressed in Xenopus laevis oocytes, the transport of glutamine or asparagine via human SN1 was associated with inward currents under voltage-clamped conditions. The transport function, monitored as glutamine-or asparagine-induced currents, was saturable, Na ؉ -dependent, Li ؉ -tolerant, and pH-sensitive. The transport cycle was associated with the involvement of more than one Na ؉ ion. Uptake of asparagine was directly demonstrable in these oocytes by using radiolabeled substrate, and this uptake was inhibited by membrane depolarization. In addition, simultaneous measurement of asparagine influx and charge influx in the same oocyte yielded an asparagine:charge ratio of 1. These data suggest that SN1 mediates the influx of two Na ؉ and one amino acid substrate per transport cycle coupled to the efflux of one H ؉ , rendering the transport process electrogenic.

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Inter‐organ metabolism of amino acids in vivo

Cited by 68 publications

References 90 publications

Direct and indirect effects of amino acids on hepatic glucose metabolism in humans

Direct and indirect effects of amino acids on hepatic glucose metabolism in humans

Amino acid ingestion improves muscle protein synthesis in the young and elderly

Primary Structure, Genomic Organization, and Functional and Electrogenic Characteristics of Human System N 1, a Na+- and H+-coupled Glutamine Transporter

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