Inhibition of hepatic gluconeogenesis and enhanced glucose uptake contribute to the development of hypoglycemia in mice bearing interleukin-1beta- secreting tumor.
Mice bearing IL-1beta-secreting tumor were used to study the chronic effect of IL-1beta on glucose metabolism. Mice were injected with syngeneic tumor cells transduced with the human IL-1beta gene. Serum IL-1beta levels increased exponentially with time. Secretion of IL-1beta from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Body composition analysis revealed that IL-1beta caused a significant loss in fat tissue without affecting lean body mass and water content. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities and mRNA levels of these enzymes were reduced, and 2-deoxy-glucose uptake by peripheral tissues was enhanced. mRNA levels of glucose transporters (Gluts) in the liver were determined by real-time PCR analysis. Glut-3 mRNA levels were up-regulated by IL-1beta. Glut-1 and Glut-4 mRNA levels in IL-1beta mice were similar to mRNA levels in pair-fed mice bearing nonsecreting tumor. mRNA level of Glut-2, the major Glut of the liver, was down-regulated by IL-1beta. We concluded that both decreased glucose production by the liver and enhanced glucose disposal lead to the development of hypoglycemia in mice bearing IL-1beta-secreting tumor. The observed changes in expression of hepatic Gluts that are not dependent on insulin may contribute to the increased glucose uptake.
Department of Medicine, Hadassah University Hospital, Mount Scopus, P.O. Box 24035, Jerusalem 91240, Israel.
Shulamit
S
Metzger
Samir
S
Nusair
David
D
Planer
Varda
V
Barash
Orit
O
Pappo
Joel
J
Shilyansky
Tova
T
Chajek-Shaul
D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001786:Blood Glucose; D001823:Body Composition; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D045744:Cell Line, Tumor; D004435:Eating; D005260:Female; D005354:Fibrosarcoma; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000493:pharmacokinetics; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D007375:Interleukin-1; D020738:Leptin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D006003:Glycogen; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose