Author/Editor     Battelino, Tadej; Goto, Masakatsu; Kržišnik, Ciril; Zeller, WP
Title     Tumor necrosis factor-alpha alters glucose metabolism in suckling rats
Type     članek
Source     J Lab Clin Med
Vol. and No.     Letnik 133, št. 6
Publication year     1999
Volume     str. 583-9
Language     eng
Abstract     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 power on 7 U/kg, intraoperationeally) the plasma glucose concentration increased from 4.1 +- 0.3 mmol/L to 6.9 +- 0.5 mmol/L (P < 0.5) at 2 hours and subsequently decreased to 1.4 +- 0.5 mmol/L (P < 0.5) at 6 hours, although plasma lactate concentration increased from 1.1 +- 0.1 mmol/L to 5.5 +- 0.3 mmol/L (P < 0.5) at 6 hours. Plasma insulin concentration remained inchanged throughout the experiment. TNF-alpha increased GLUT 1 messenger RNA (mRNA) abundance in the brain. liver, muscle, and fatty tissue (P < 0.5). Glucose uptake increased in association with the increase of GLUT 1 mRNA abundance. TNF-alpha decreased mRNA abundance of GLUT 2 and phosphoenolpyruvate carboxykinase (PECK) 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.
Descriptors     TUMOR NECROSIS FACTOR
GLUCOSE
ANIMALS, SUCKLING
BLOOD GLUCOSE
GENE EXPRESSION REGULATION, DEVELOPMENTAL
INDOMETHACIN
INSULIN
LACTIC ACID
ORGAN SPECIFICITY
PHOSPHOENOLPYRUVATE CARBOXYKINASES
RATS, SPRAGUE-DAWLEY
RNA, MESSENGER