Tumor necrosis factor-alpha alters glucose metabolism in suckling rats.
Tumor necrosis factor-alpha (TNF-alpha), an important mediator of endotoxic shock, induces hypoglycemia and shock in adult animals. Indomethacin ameliorates TNF-alpha-induced hypoglycemia in the adult. However, effects of TNF-alpha on glucose metabolism in the newborn have not been well documented. The present study showed that in 10-day-old rats injected with TNF-alpha (4.5 x 10(7) U/kg, intraperitoneally) the plasma glucose concentration increased from 4.1 +/- 0.3 mmol/L to 6.9 +/- 0.5 mmol/L (P < .05) at 2 hours and subsequently decreased to 1.4 +/- 0.5 mmol/L (P < .05) at 6 hours, although plasma lactate concentration increased from 1.1 +/- 0.1 mmol/L to 5.5 +/- 0.3 mmol/L (P < .05) at 6 hours. Plasma insulin concentration remained unchanged throughout the experiment. TNF-alpha increased GLUT 1 messenger RNA (mRNA) abundance in the brain, liver, muscle, and fatty tissue (P < .05). Glucose uptake increased in association with the increase of GLUT1 mRNA abundance. TNF-alpha decreased mRNA abundance of GLUT 2 and phosphoenolpyruvate carboxykinase (PEPCK) in liver, suggesting decreased gluconeogenesis. Indomethacin (1.5 mg/kg 20 minutes before TNF-alpha, intraperitoneally) attenuated the hypoglycemia, the lactacidemia, and the increase of GLUT1 mRNA abundance and glucose uptake. Indomethacin attenuated the decrease of PEPCK mRNA abundance. We concluded that TNF-alpha induced hypoglycemia, increasing GLUT1 mRNA abundance and glucose uptake and decreasing PEPCK mRNA abundance in 10-day-old rats. Indomethacin attenuated the TNF-alpha-induced glucose dyshomeostasis.
Battelino
T
T
Department of Pediatrics, University Medical Center Ljubljana, Slovenia.
Goto
M
M
Krzisnik
C
C
Zeller
W P
WP
D000818:Animals; D000833:Animals, Suckling; D001786:Blood Glucose / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose; D007213:Indomethacin