Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients

Livio Luzi, Alberto Battezzati, Gianluca Perseghin, Elda Bianchi, Ileana Terruzzi, Donatella Spotti, Sandro Vergani, Antonio Secchi, Ennio La Rocca, Giovanni Ferrari, Carlo Staudacher, Renato Castoldi, Valerio Di Carlo, Guido Pozza

Research output: Contribution to journalArticle

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Abstract

In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8±2.8 vs. 6.8±1.1 μU/ml, P <0.01) (107±17 vs. 41±7 pM); (b) reduced plasma leucine (92±9 vs. 124±2 μM, P <0.05), branched chain amino acids (BCAA) (297±34 vs. 416±10 μM, P <0.05), endogenous leucine flux (ELF) (28.7±0.8 vs. 39.5±0.7 μmol · m-2 · min-1, P <0.01) and nonoxidative leucine disposal (NOLD) (20.7±0.2 vs. 32.0±0.7 μmol · m-2 · min-1, P <0.01); (c) similar leucine oxidation (LO) (8.0±0.1 vs. 7.5±0.1 μmol · m-2 · min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116±5 and 107±9 μM), ELF (38.1±0.1 and 38.5±0.9 μmol · m-2 · min-1), and NOLD (28.3±0.6 and 31.0±1.3 μmol · m-2 · min-1) (P = NS vs. CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P <0.05), BCAA (38% vs. 47%, P <0.05), ELF (28% vs. 33%, P <0.05), and LO (0% vs. 32%, P <0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P <0.05 vs. CON) by insulin. Combined kidney and pancreas transplantation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9±0.7 vs. 36.1±0.8 μmol · m-2 · min-1, P <0.01 compared to CON), which was normalized by transplantation (44.3±0.8 μmol · m-2 · min-1).

Original languageEnglish
Pages (from-to)1948-1958
Number of pages11
JournalJournal of Clinical Investigation
Volume93
Issue number5
Publication statusPublished - May 1994

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Pancreas Transplantation
Leucine
Kidney Transplantation
Insulin
Proteins
Hyperinsulinism
Branched Chain Amino Acids
Transplants
Kidney
Amino Acids
Indirect Calorimetry

Keywords

  • diabetes mellitus
  • kidney transplant
  • kidney-pancreas transplant
  • protein turnover
  • uremia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients. / Luzi, Livio; Battezzati, Alberto; Perseghin, Gianluca; Bianchi, Elda; Terruzzi, Ileana; Spotti, Donatella; Vergani, Sandro; Secchi, Antonio; La Rocca, Ennio; Ferrari, Giovanni; Staudacher, Carlo; Castoldi, Renato; Di Carlo, Valerio; Pozza, Guido.

In: Journal of Clinical Investigation, Vol. 93, No. 5, 05.1994, p. 1948-1958.

Research output: Contribution to journalArticle

Luzi, L, Battezzati, A, Perseghin, G, Bianchi, E, Terruzzi, I, Spotti, D, Vergani, S, Secchi, A, La Rocca, E, Ferrari, G, Staudacher, C, Castoldi, R, Di Carlo, V & Pozza, G 1994, 'Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients', Journal of Clinical Investigation, vol. 93, no. 5, pp. 1948-1958.
Luzi, Livio ; Battezzati, Alberto ; Perseghin, Gianluca ; Bianchi, Elda ; Terruzzi, Ileana ; Spotti, Donatella ; Vergani, Sandro ; Secchi, Antonio ; La Rocca, Ennio ; Ferrari, Giovanni ; Staudacher, Carlo ; Castoldi, Renato ; Di Carlo, Valerio ; Pozza, Guido. / Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 5. pp. 1948-1958.
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T1 - Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients

AU - Luzi, Livio

AU - Battezzati, Alberto

AU - Perseghin, Gianluca

AU - Bianchi, Elda

AU - Terruzzi, Ileana

AU - Spotti, Donatella

AU - Vergani, Sandro

AU - Secchi, Antonio

AU - La Rocca, Ennio

AU - Ferrari, Giovanni

AU - Staudacher, Carlo

AU - Castoldi, Renato

AU - Di Carlo, Valerio

AU - Pozza, Guido

PY - 1994/5

Y1 - 1994/5

N2 - In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8±2.8 vs. 6.8±1.1 μU/ml, P <0.01) (107±17 vs. 41±7 pM); (b) reduced plasma leucine (92±9 vs. 124±2 μM, P <0.05), branched chain amino acids (BCAA) (297±34 vs. 416±10 μM, P <0.05), endogenous leucine flux (ELF) (28.7±0.8 vs. 39.5±0.7 μmol · m-2 · min-1, P <0.01) and nonoxidative leucine disposal (NOLD) (20.7±0.2 vs. 32.0±0.7 μmol · m-2 · min-1, P <0.01); (c) similar leucine oxidation (LO) (8.0±0.1 vs. 7.5±0.1 μmol · m-2 · min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116±5 and 107±9 μM), ELF (38.1±0.1 and 38.5±0.9 μmol · m-2 · min-1), and NOLD (28.3±0.6 and 31.0±1.3 μmol · m-2 · min-1) (P = NS vs. CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P <0.05), BCAA (38% vs. 47%, P <0.05), ELF (28% vs. 33%, P <0.05), and LO (0% vs. 32%, P <0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P <0.05 vs. CON) by insulin. Combined kidney and pancreas transplantation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9±0.7 vs. 36.1±0.8 μmol · m-2 · min-1, P <0.01 compared to CON), which was normalized by transplantation (44.3±0.8 μmol · m-2 · min-1).

AB - In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8±2.8 vs. 6.8±1.1 μU/ml, P <0.01) (107±17 vs. 41±7 pM); (b) reduced plasma leucine (92±9 vs. 124±2 μM, P <0.05), branched chain amino acids (BCAA) (297±34 vs. 416±10 μM, P <0.05), endogenous leucine flux (ELF) (28.7±0.8 vs. 39.5±0.7 μmol · m-2 · min-1, P <0.01) and nonoxidative leucine disposal (NOLD) (20.7±0.2 vs. 32.0±0.7 μmol · m-2 · min-1, P <0.01); (c) similar leucine oxidation (LO) (8.0±0.1 vs. 7.5±0.1 μmol · m-2 · min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116±5 and 107±9 μM), ELF (38.1±0.1 and 38.5±0.9 μmol · m-2 · min-1), and NOLD (28.3±0.6 and 31.0±1.3 μmol · m-2 · min-1) (P = NS vs. CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P <0.05), BCAA (38% vs. 47%, P <0.05), ELF (28% vs. 33%, P <0.05), and LO (0% vs. 32%, P <0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P <0.05 vs. CON) by insulin. Combined kidney and pancreas transplantation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9±0.7 vs. 36.1±0.8 μmol · m-2 · min-1, P <0.01 compared to CON), which was normalized by transplantation (44.3±0.8 μmol · m-2 · min-1).

KW - diabetes mellitus

KW - kidney transplant

KW - kidney-pancreas transplant

KW - protein turnover

KW - uremia

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