Effects of long-term administration of recombinant bovine tumor necrosis factor-alpha on glucose metabolism and growth hormone secretion in steers.
OBJECTIVE
To investigate the effects of long-term administration of recombinant bovine tumor necrosis factor-alpha (rbTNF) on plasma glucose and growth hormone concentrations, and to determine whether treatment with rbTNF causes insulin resistance in steers.


METHODS
5 steers treated with rbTNF and 5 steers treated with saline (0.9% NaCl) solution (control).


METHODS
In experiment 1, rbTNF (5.0 microg/kg of body weight) or saline solution (5 ml) was administered SC daily for 12 days. Blood samples were obtained before treatment, and plasma was harvested for determination of glucose, insulin, and growth hormone (GH) concentrations. In experiment 2, insulin, glucose, or growth hormone-releasing hormone (GHRH) was administered IV on days 7, 9, and 11, respectively, after initiation of rbTNF or saline treatment in experiment 1. Plasma glucose and insulin concentrations were measured before and at various times for 4 hours after insulin or glucose administration. Plasma GH concentrations were measured at various times for 3 hours after GHRH administration.


RESULTS
In experiment 1, administration of rbTNF resulted in hyperinsulinemia without hypoglycemia and decreased plasma GH concentrations. In experiment 2, plasma glucose concentrations were higher in steers treated with rbTNF and insulin than in controls. Plasma GH concentrations were lower in steers treated with rbTNF and GHRH than in controls.


CONCLUSIONS
Prolonged treatment with rbTNF induced insulin resistance and inhibited GHRH-stimulated release of GH in steers. Results indicate that rbTNF is a proximal mediator of insulin resistance and inhibits release of GH during periods of endotoxemia or infection.
Kushibiki
S
S
Department of Animal Production, Tohoku National Agricultural Experimental Station, Iwate, Japan.
Hodate
K
K
Shingu
H
H
Ueda
Y
Y
Mori
Y
Y
Itoh
T
T
Yokomizo
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002417:Cattle / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D005947:Glucose