Splanchnic Amino Acid and Glucose Metabolism During Amino Acid Infusion in Dogs

Ferrannini, Eleuterio; DeFronzo, Ralph A.; Gusberg, Richard; Tepler, Jeffery; Jacob, Ralph; Aaron, Michael; Smith, Douglas J.; Barrett, Eugene J.

doi:10.2337/diab.37.2.237

Cited by 20 publications

(9 citation statements)

References 21 publications

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“…These results are in line with studies in dogs that have shown that infusion of AA, which were disposed by about 90% into the splanchnic tissues, inducing a rise in hepatic glucose production [44]. Thus, direct effects of AA on GNG are likely explained by increased supply of gluconeogenic substrates.…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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

et al. 2003

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“…The concentration of glycine required to provoke the tight binding of folylpolyglutamates to serine hydroxymethyltransferase is 0.1 m M , well below the actual concentration of free glycine in rat liver (5 mM) (24). The concentration of plasma glycine in the human (25,26), dog (27), and rat (24,28), is about 0.2 mM, while that in the pig is higher (1.0 mM) (29) . This suggests that the concentration of glycine in pig liver is at least 1.0 mM.…”

Section: The Major Folate Binding Proteinsmentioning

confidence: 83%

Pteridines, XCIII. Reactions of 6-Chloro-, 7 -Chloro- and 6,7-Dichloro-1,3-dimethyllumazines with N-Nucleophiles

1989

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“…Although the above suggests skeletal muscle to be the major site for glutamine synthesis during amino acid infusion, it is not likely to be the predominant contributor. Studies in human adults show that only 25-30% of infused amino acid nitrogen is taken up by the skeletal muscle and 70% is removed by the splanchnic compartment (23,27,28). Thus, it is likely that the observed increase in Ra of glutamine in response to increased amino acid infusion is contributed by both the skeletal muscle as well as by the splanchnic organs.…”

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confidence: 98%

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

et al. 2005

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Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5][6][7][8][9][10][11][12][13][14][15] 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis. Glutamine participates in a number of key metabolic processes (1) and is also proposed to play an important role in enhancing immune function (2-4). A decrease in plasma glutamine concentration in response to stress (acute illness, burns, trauma, etc.) suggests that the rate of DGln is unable to keep pace with the rate of utilization/requirement. This has led several investigators to suggest that glutamine is a conditionally essential amino acid. Studies in adults show that parenteral nutrition supplemented with glutamine decreased both the morbidity and mortality (5,6).Because the concentration of plasma glutamine is lower in VLBW infants, and the currently used parenteral nutrient solutions do not contain glutamine, VLBW premature infants were identified as another group of subjects who could potentially benefit from supplementation of enteral and parenteral nutrition with glutamine (7-9). However, whether provision of a higher amount of parenteral amino acids to these VLBW infants enhances the rate of DGln has not been examined.Glutamine is synthesized by transamination of ␣-ketoglutarate to glutamate and conversion of glutamate to glutamine. The latter reaction is catalyzed by glutamine synthase. The sources of carbon skeleton for the synthesis of glutamine, i.e. glutamate and ␣-ketoglutarate, are derived from the amino acids entering the TCA cycle (anaplerosis). An increase influx of these amino acids would be anticipated to result in an increase in DGln (cataplerosis) (10). Studies in human adults show that supplementation of parenteral nutrition with analogues of ␣-ketoglutarate enhances the intracellular pool of glutamine in the muscle (11,12). We have previously shown that th...

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Splanchnic Amino Acid and Glucose Metabolism During Amino Acid Infusion in Dogs

Cited by 20 publications

References 21 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

Pteridines, XCIII. Reactions of 6-Chloro-, 7 -Chloro- and 6,7-Dichloro-1,3-dimethyllumazines with N-Nucleophiles

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

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