Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients.
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 microU/ml, P < 0.01) (107 +/- 17 vs. 41 +/- 7 pM); (b) reduced plasma leucine (92 +/- 9 vs. 124 +/- 2 microM, P < 0.05), branched chain amino acids (BCAA) (297 +/- 34 vs. 416 +/- 10 microM, P < 0.05), endogenous leucine flux (ELF) (28.7 +/- 0.8 vs. 39.5 +/- 0.7 mumol.m-2.min-1, P < 0.01) and nonoxidative leucine disposal (NOLD) (20.7 +/- 0.2 vs. 32.0 +/- 0.7 mumol.m-2. min-1, P < 0.01); (c) similar leucine oxidation (LO) (8.0 +/- 0.1 vs. 7.5 +/- 0.1 mumol.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 microM), ELF (38.1 +/- 0.1 and 38.5 +/- 0.9 mumol.m-2.min-1), and NOLD (28.3 +/- 0.6 and 31.0 +/- 1.3 mumol.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 transplanation 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 mumol.m-2.min-1, P < 0.01 compared to CON), which was normalized by transplantation (44.3 +/- 0.8 mumol.m-2.min-1).
Luzi
L
L
Department of Internal Medicine, San Raphael Scientific Institute, University of Milan, Italy.
Battezzati
A
A
Perseghin
G
G
Bianchi
E
E
Terruzzi
I
I
Spotti
D
D
Vergani
S
S
Secchi
A
A
La Rocca
E
E
Ferrari
G
G
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006728:Hormones / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007165:Immunosuppression Therapy; D007651:Keto Acids / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation / Q000502:physiology*; D007930:Leucine / Q000493:pharmacokinetics*; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D016035:Pancreas Transplantation / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D014511:Uremia / Q000628:therapy*; D015866:Uveitis, Posterior / Q000378:metabolism
D001786:Blood Glucose; D006454:Hemoglobins; D006728:Hormones; D007651:Keto Acids; D011506:Proteins; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D009584:Nitrogen