Glucose and amino acid metabolism in chronic renal failure: Effect of insulin and amino acids

Pietro Castellino, Anna Solini, Livio Luzi, J. Grant Barr, Douglas J. Smith, Alexander Petrides, Mauro Giordano, Chris Carroll, Ralph A. DeFronzo

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82 Scopus citations


The effects of hy-perinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [l-14C]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 ± 0.50 vs. 6.76 ± 0.73 mg·kg-1·min-1, P < 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 ± 0.70 vs. 4.32 ± 0.60 mg·kg-1·min-1, P < 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 ± 0.06 vs. 1.75 ± 0.06), leucine oxidation (0.25 ± 0.01 vs. 0.30 ± 0.01), and nonoxidative leucine disposal (1.29 ± 0.06 vs. 1.40 ± 0.07 μmol·kg-1·min-1) were reduced in CRF vs. control subjects (all P < 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (MOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 ± 0.11 vs. 2.10 ± 0.10 μmol·kg-1min-1 P < 0.01) and net leucine balance (0.27 ± 0.05 vs. 0.41 ± 0.05, P < 0.05) was reduced in CRF patients. In summary, in patients with CRF 1 ) basal leucine turnover and oxidation are reduced, 2) insulin-mediated suppression of proteolysis and net leucine flux into protein are normal, 3) amino acid-induced stimulation of protein synthesis and net flux of leucine into protein are impaired, and 4) insulin-mediated stimulation of glucose metabolism is reduced because of diminished nonoxidative glucose disposal. These results demonstrate a clear-cut dissociation between the effects of insulin on glucose vs. amino acid-protein metabolism, and an impairment in amino acid-induced stimulation of protein anabolism.

Original languageEnglish (US)
Pages (from-to)F168-F176
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number2
StatePublished - 1992


  • Protein metabolism

ASJC Scopus subject areas

  • Physiology


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