Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects

Lochs, Herbert; Hübl, Wolfgang; Gasić, S; Roth, E.; Morse, Emile L.; Adibi, S. A.

doi:10.1152/ajpendo.1992.262.2.e155

Cited by 14 publications

(9 citation statements)

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“…Our net renal balance data for alanine, glycerol, and glutamine are in general agreement with previous reports (9,12,16,31,49,50). Our data for renal lactate net uptake (ϳ170 mol/min) are essentially identical to those reported by Cersosimo and colleagues (9, 12) (ϳ170 mol/min).…”

Section: Discussionsupporting

confidence: 92%

Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Meyer¹,

Stümvoll²,

Dostou³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

129

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. Renal substrate exchange and gluconeogenesis in normal postabsorptive humans. Am J Physiol Endocrinol Metab 282: E428-E434, 2002. First published October 23, 2001 10.1152/ ajpendo.00116.2001.-Release of glucose by the kidney in postabsorptive normal humans is generally regarded as being wholly due to gluconeogenesis. Although lactate is the most important systemic gluconeogenic precursor and there is appreciable net renal lactate uptake, renal lactate gluconeogenesis has not yet been investigated. The present studies were therefore undertaken to quantitate the contribution of lactate to renal gluconeogenesis and the role of the kidney in lactate metabolism. We determined systemic and renal lactate conversion to glucose as well as renal lactate net balance, fractional extraction, uptake, and release in 24 postabsorptive humans by use of a combination of isotopic and renal balance techniques. For comparative purposes, accumulated similar data for glutamine, alanine, and glycerol are also reported. Systemic lactate gluconeogenesis (1.97 Ϯ 0.12 mol⅐kg Ϫ1 ⅐min Ϫ1) was about threefold greater than that from glycerol, glutamine, and alanine. The sum of gluconeogenesis from these precursors, uncorrected for tricarboxylic acid (TCA) cycle carbon exchange, explained 34% of systemic glucose release. Renal lactate uptake (3.33 Ϯ 0.28 mol⅐kg Ϫ1 ⅐min Ϫ1) accounted for nearly 30% of its systemic turnover. Renal gluconeogenesis from lactate (0.78 Ϯ 0.10 mol⅐kg Ϫ1 ⅐min Ϫ1 ) was 3.5, 2.5, and 9.6-fold greater than that from glycerol, glutamine, and alanine. The sum of renal gluconeogenesis from these precursors equaled ϳ40% of the sum of their systemic gluconeogenesis. When the isotopically determined rates of systemic and renal gluconeogenesis were corrected for TCA cycle carbon exchange, gluconeogenesis from these precursors accounted for 43% of systemic glucose release and 89% of renal glucose release. We conclude that 1) in postabsorptive normal humans, lactate is the dominant precursor for both renal and systemic gluconeogenesis; 2) the kidney is an important organ for lactate disposal; 3) under these conditions, renal glucose release is predominantly, if not exclusively, due to gluconeogenesis; and 4) liver and kidney are similarly important for systemic gluconeogenesis. glutamine; alanine; glycerol; lactate; kidney RELEASE OF GLUCOSE BY THE KIDNEY has been reported to account on average for ϳ20% of all glucose released into the circulation in postabsorptive healthy humans (7-11, 16, 35-38, 45-47). Because the kidney normally stores little glycogen and its cells that could store glycogen lack glucose-6-phosphatase, renal glucose release is generally thought to be predominantly, if not exclusively, due to gluconeogenesis. At the present time, however, there is relatively little information available on the substrates used for gluconeogenesis by the human kidney. In studies of small numbers of postabsorptive normal volunteers, conversion of glutamine (34, 35, 47), glycerol (7), and alanine (47) to glucose has been found to...

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Section: Discussionsupporting

confidence: 92%

Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Meyer¹,

Stümvoll²,

Dostou³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

129

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“…The participation of individual organs in the disappearance of glutamine dipeptides has also been investigated by Abumrad et a126 in dogs and by Lochs et al2l,28 in humans. In humans, as in dogs, the kidneys, muscle, and splanchnic organs participated in the removal of dipeptides (Fig 8).…”

Section: Fate Of Intravenously Administered Dipeptidesmentioning

confidence: 95%

Invited Review: Dipeptides in Parenteral Nutrition: From Basic Science to Clinical Applications

1993

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The use of intravenous dipeptides shows great promise as an avenue for the provision of amino acids that may otherwise be difficult to deliver via nutrient infusions. The physical/chemical properties and metabolism of numerous dipeptides have now been explored in experimental and human studies. It has been found that these agents have the capacity to spare nitrogen and support serum protein levels in a fashion equivalent to that of intravenous free amino acids. An additional benefit is the ability to deliver certain amino acids that are relatively unstable or poorly soluble in aqueous solutions. These various aspects of intravenous dipeptides are considered in this review.

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“…Whether these cis elements play a role in controlling gene expression in the kidney in response to cellular availability of free amino acids and dipeptides needs to be determined. However, studies in humans suggest that starvation reduces renal peptide transport activity, as demonstrated by a reduction in removal of the intravenously infused dipeptide Gly-Gln by the kidney (4,42). In the yeast Saccharomyces cerevisiae, gene expression of Ptr-2, the yeast peptide transporter (50), is upregulated at the expression level by selected dipeptides that activate an ubiquitin-dependent proteolytic pathway (69).…”

Section: Regulation Of Expression Level and Transport Activity Of Pepmentioning

confidence: 99%

An update on renal peptide transporters

Daniel

Rubio‐Aliaga

2003

American Journal of Physiology-Renal Physiology

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Daniel, Hannelore, and Isabel Rubio-Aliaga. An update on renal peptide transporters. Am J Physiol Renal Physiol 284: F885-F892, 2003; 10.1152/ajprenal.00123.2002The brush-border membrane of renal epithelial cells contains PEPT1 and PEPT2 proteins that are rheogenic carriers for short-chain peptides. The carrier proteins display a distinct surface expression pattern along the proximal tubule, suggesting that initially di-and tripeptides, either filtered or released by surface-bound hydrolases from larger oligopeptides, are taken up by the low-affinity but high-capacity PEPT1 transporter and then by PEPT2, which possesses a higher affinity but lower transport capacity. Both carriers transport essentially all possible di-and tripeptides and numerous structurally related drugs. A unique feature of the mammalian peptide transporters is the capability of proton-dependent electrogenic cotransport of all substrates, regardless of their charge, that is achieved by variable coupling in proton movement along with the substrate down the transmembrane potential difference. This review focuses on the postcloning research efforts to understand the molecular physiology of peptide transport processes in renal tubules and summarizes available data on the underlying genes, protein structures, and transporter function as derived from studies in heterologous expression systems. PEPT1; PEPT2; renal physiology; localization; functional analysis RENAL TUBULAR PEPTIDE TRANSPORT activity was originally discovered after intravenous infusion of the resistant dipeptide Gly-Sar in rats that resulted in a high accumulation of the intact dipeptide in renal tissue (1, 3). Studies with renal brush-border membrane vesicles established that renal apical peptide uptake was an electrogenic, proton-dependent uphill transport process for di-and tripeptides and related drugs mediated by two kinetically different systems (for a review, see Ref. 38). The underlying proteins, differing in transport characteristics, now designated as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), have been identified, and the corresponding genes have been cloned from a variety of species (10,24,25,39,41,(52)(53)(54). The transporters have been expressed in various cellular models, and information on structure, transport function, and regulation has been gathered by flux studies and electrophysiological techniques. Expression analysis of transporter mRNA and protein by in situ hybridization and immunohistochemistry has extended our knowledge of tissue distribution, particularly the renal zonation of PEPT1 and PEPT2 surface expression. THE MOLECULAR ENTITIES OF APICAL PEPTIDE TRANSPORTPEPT1 and PEPT2 are polytopic integral membrane proteins with 12 predicted membrane-spanning domains and NH 2 -and COOH-terminal ends facing the cytosol. Transporter architecture and membrane topology have not been studied systematically, and therefore structural information is still mainly based on hydropathic analysis of amino acid sequences. The mammalian PEPT1 proteins comprise 701-710 amino acids, ...

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Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects

Cited by 14 publications

References 1 publication

Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

Invited Review: Dipeptides in Parenteral Nutrition: From Basic Science to Clinical Applications

An update on renal peptide transporters

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