Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat.
We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U-14C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection.
Laboratory of Nutrition/Infection Cancer Research Institute, New England Deaconess Hospital, Harvard Medical School, Boston, MA.
E A
EA
Flores
N
N
Istfan
J J
JJ
Pomposelli
G L
GL
Blackburn
B R
BR
Bistrian
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D005934:Glucagon