Influence of insulin on leucine kinetics in the whole body and across the forearm in post-absorptive insulin dependent diabetic (type 1) patients.
Acute effects of insulin on protein metabolism (whole body and forearm muscle) were simultaneously assessed using doubly labelled (13C15N) leucine in post-absorptive Type I diabetic patients. Whole body protein kinetics were calculated using either plasma 13C leucine or alpha-ketoisocaproic acid (alpha-KIC) enrichment to represent labelling of the precursor pool. Forearm muscle protein metabolism was measured using a previously described arterio-venous model. Acute insulin infusion (2-3 units per hour) for 2-3 hours reduced whole body protein breakdown (p < 0.01), synthesis (p < 0.05) and oxidation (p < 0.05) irrespective of the basis of calculation. Across forearm muscle, insulin reduced overall net negative protein balance (p < 0.05) by inhibiting protein breakdown, 80% and synthesis, 71%. Insulin reduced the deamination of leucine to alpha-KIC (p < 0.05) and its reamination (p < 0.05). This study demonstrates that whole body protein metabolism is broadly paralleled by events in skeletal muscle though the forearm approach is considerably more sensitive to noise than whole body protein kinetic measurements. This results from the less damped nature of the forearm model and the necessity to measure a greater number of variables required to solve the appropriate balance equations. Failure of insulin per se to promote protein synthesis in man is not model dependent and suggests that the observed differences relating to insulin mediated control of protein kinetics found in man compared with small mammals are both real and species related.
Pacy
P J
PJ
Nutrition Research Group, Clinical Research Centre, Harrow, UK.
Bannister
P A
PA
Halliday
D
D
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005542:Forearm / Q000098:blood supply; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007553:Isotope Labeling / Q000379:methods; D007657:Ketone Bodies / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000378:metabolism*; D008297:Male; D009587:Nitrogen Isotopes; D010101:Oxygen Consumption; D011506:Proteins / Q000378:metabolism*
D001786:Blood Glucose; D002247:Carbon Isotopes; D007328:Insulin; D007657:Ketone Bodies; D009587:Nitrogen Isotopes; D011506:Proteins; D005934:Glucagon; D007930:Leucine