scholarly journals Inability to stimulate skeletal muscle or whole body protein synthesis in Type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine

Diabetologia ◽  
1990 ◽  
Vol 33 (1) ◽  
pp. 43-51 ◽  
Author(s):  
W. M. Bennet ◽  
A. A. Connacher ◽  
K. Smith ◽  
R. T. Jung ◽  
M. J. Rennie
1989 ◽  
Vol 76 (4) ◽  
pp. 447-454 ◽  
Author(s):  
W. M. Bennet ◽  
A. A. Connacher ◽  
C. M. Scrimgeour ◽  
K. Smith ◽  
M. J. Rennie

1. Anterior tibial muscle protein synthesis in seven healthy postabsorptive men was determined from increases in muscle protein bound leucine enrichment during a primed continuous infusion of l-[1−13C]leucine. Biopsies were taken 30 min after the beginning of leucine infusion (when plasma 13C enrichment was steady), 240 min later during continued fasting and again after 240 min of infusion of a mixed amino acid solution which increased plasma total amino acid concentrations by 37%. The mean enrichment of 13C in plasma α-ketoisocaproate was used as an index of the enrichment of the precursor pool for leucine metabolism. 2. Anterior tibial muscle mixed protein synthetic rate during fasting was 0.055 (sd 0.008) %/h and this increased by an average of 35% during infusion of mixed amino acid to 0.074 (sd 0.021) %/h (P < 0.05). 3. Whole-body protein breakdown (expressed as the rate of endogenous leucine appearance in plasma) was 121 (sd 8) μmol h−1 kg−1 during fasting and decreased (P < 0.01) by an average of 12% during amino acid infusion. Leucine oxidation was 18 (sd 3) μmol h−1 kg−1 during fasting and increased (P < 0.001) by 89% during amino acid infusion. Whole-body protein synthesis (non-oxidative leucine disappearance) was 104 (sd 6) μmol h−1 kg−1 during fasting and rose by 13% (P < 0.001) during mixed amino acid infusion. 4. 13C enrichment of muscle free leucine was only 61 (sd 19) % of that in plasma α-ketoisocaproate and this increased to 74 (sd 16) % (P < 0.02) during mixed amino acid infusion. 5. The results suggest that increased availability of amino acids reverses whole-body protein balance from negative to positive and a major component of this is the increase in muscle protein synthesis.


1991 ◽  
Vol 80 (4) ◽  
pp. 345-352 ◽  
Author(s):  
P. J. Pacy ◽  
G. N. Thompson ◽  
D. Halliday

1. The aims of this study were twofold: (i) to investigate the ability of a recently described [2H5]phenylalanine method for quantifying whole-body protein turnover during acute physiological perturbation; (ii) to determine specifically whether the previously observed increase in protein synthesis on insulin withdrawal in insulin-dependent (type 1) diabetic patients seen when employing the [13C]leucine technique could be corroborated by using [2H5]phenylalanine. 2. Whole-body protein turnover was measured by both the [2H5]phenylalanine and [13C]leucine primed continuous infusion methods applied simultaneously to six type I post-absorptive diabetic patients during insulin withdrawal and infusion. 3. Values were determined by the [13C]leucine method by measuring either [13C]leucine (primary pool) or α-[13C]ketoisocaproic acid (reciprocal pool) enrichment in plasma. 4. Values of whole-body protein breakdown during insulin withdrawal derived from the [2H5]phenylalanine and primary and reciprocal pool [13C]leucine models respectively were 3.54 ± 0.43, 3.85 ± 0.41 and 4.62 ± 0.44 g day−1 kg−1 (means ± SD). Insulin infusion resulted in a significant reduction (P <0.02) to 3.07 ± 0.34, 3.05 ± 0.26 and 3.82 ± 0.4 g day−1 kg−1, respectively. Synthesis values fell significantly but by a smaller amount than breakdown, resulting in increased (P <0.05) net protein deposition, regardless of the model used. 5. These data demonstrate that the [2H5]phenylalanine and [13C]leucine methods generate similar results both in absolute and relative terms in response to short-term insulin infusion. 6. The confirmation of increased whole-body protein synthesis during insulin withdrawal by two independent methods supports the validity of this observation.


Diabetologia ◽  
1986 ◽  
Vol 29 (6) ◽  
pp. 358-361 ◽  
Author(s):  
K. Hermansen ◽  
O. Rasmussen ◽  
J. Arnfred ◽  
E. Winther ◽  
O. Schmitz

1987 ◽  
Vol 72 (1) ◽  
pp. 123-130 ◽  
Author(s):  
J. Kastrup ◽  
T. Nørgaard ◽  
H.-H. Parving ◽  
N. A. Lassen

1. The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic subjects. 2. Blood flow was measured by the local 133Xexenon washout technique in a vascular bed locally paralysed by the injection of histamine. Blood flow was measured before, during and after a 40 mmHg increase of the vascular transmural pressure, induced by head-up tilt. 3. The mean increase in blood flow during headup tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P < 0.0005 and P < 0.05, respectively). 4. An inverse correlation between microvascular distensibility and degree of hyalinosis of the terminal arterioles in biopsies from the skin was demonstrated (r = − 0.57, P < 0.001). 5. Our results suggest that terminal arteriolar hyalinosis reduces the microvascular distensibility and probably increases the minimal vascular resistance, thereby impeding hyperaemic responses.


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