Insulin-like growth factor-I and insulin reduce leucine flux and oxidation in conscious tumor necrosis factor-infused dogs.
BACKGROUND
We have tested the hypothesis that insulin-like growth factor-I (IGF-I) or insulin can prevent the protein catabolic effects of tumor necrosis factor (TNF).


METHODS
After a 2-hour basal period TNF was infused (prime, 2.5 micrograms.kg-1; constant, 31.25 ng.kg-1.min-1) for 4 hours into conscious dogs to create the catabolic state. After 2 hours of TNF infusion either recombinant human IGF-I (n = 5) or recombinant human insulin (n = 5) was infused for an additional 2 hours. A third group (n = 5) received TNF alone for 4 hours.


RESULTS
TNF infusion caused an increase in both glucose production, reflected by [6,6-d2]glucose tracer data, and net protein catabolism, reflected by both [1-13C]leucine and [15N2]urea tracer methods. IGF-I and insulin both significantly reduced the rates of appearance of leucine and leucine oxidation to a similar extent, resulting in the significant decrease in net protein catabolism.


CONCLUSIONS
IGF-I and insulin can ameliorate the catabolic effects of TNF on protein and glucose metabolism equally effectively, although more IGF-I is required on a molar basis.
Sakurai
Y
Y
Metabolism Unit, Shriners Burns Institute, Galveston, TX 77555-1220.
Zhang
X J
XJ
Wolfe
R R
RR
D000818:Animals; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D007930:Leucine / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014508:Urea / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D014508:Urea; D005934:Glucagon; D007930:Leucine; D005947:Glucose