PMID- 8182126
OWN - NLM
STAT- MEDLINE
DCOM- 19940614
LR  - 20211203
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 93
IP  - 5
DP  - 1994 May
TI  - Combined pancreas and kidney transplantation normalizes protein metabolism in 
      insulin-dependent diabetic-uremic patients.
PG  - 1948-58
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 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).
FAU - Luzi, L
AU  - Luzi L
AD  - Department of Internal Medicine, San Raphael Scientific Institute, University of 
      Milan, Italy.
FAU - Battezzati, A
AU  - Battezzati A
FAU - Perseghin, G
AU  - Perseghin G
FAU - Bianchi, E
AU  - Bianchi E
FAU - Terruzzi, I
AU  - Terruzzi I
FAU - Spotti, D
AU  - Spotti D
FAU - Vergani, S
AU  - Vergani S
FAU - Secchi, A
AU  - Secchi A
FAU - La Rocca, E
AU  - La Rocca E
FAU - Ferrari, G
AU  - Ferrari G
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Blood Glucose)
RN  - 0 (Hemoglobins)
RN  - 0 (Hormones)
RN  - 0 (Keto Acids)
RN  - 0 (Proteins)
RN  - 816-66-0 (alpha-ketoisocaproic acid)
RN  - GMW67QNF9C (Leucine)
RN  - N762921K75 (Nitrogen)
SB  - IM
MH  - Adult
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 1/*therapy
MH  - Female
MH  - Hemoglobins/analysis
MH  - Hormones/blood
MH  - Humans
MH  - Hyperinsulinism/metabolism
MH  - Immunosuppression Therapy
MH  - Keto Acids/analysis
MH  - Kidney Failure, Chronic/*therapy
MH  - Kidney Transplantation/*physiology
MH  - Leucine/*pharmacokinetics
MH  - Male
MH  - Nitrogen/metabolism
MH  - Oxidation-Reduction
MH  - Pancreas Transplantation/*physiology
MH  - Proteins/metabolism
MH  - Uremia/*therapy
MH  - Uveitis, Posterior/metabolism
PMC - PMC294302
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
PMCR- 1994/05/01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
PHST- 1994/05/01 00:00 [pmc-release]
AID - 10.1172/JCI117186 [doi]
PST - ppublish
SO  - J Clin Invest. 1994 May;93(5):1948-58. doi: 10.1172/JCI117186.