Inhibition of Hepatic Gluconeogenesis and Enhanced Glucose Uptake Contribute to the Development of Hypoglycemia in Mice Bearing Interleukin-1β- Secreting Tumor

Shulamit Metzger, Samir Nusair, David Planer, Varda Barash, Orit Pappo, Joel Shilyansky, Tova Chajek-Shaul
2004 Endocrinology  
Mice bearing interleukin-1 (IL-1 )-secreting tumor were used to study the chronic effect of IL-1 on glucose metabolism. Mice were injected with syngeneic tumor cells transduced with the human IL-1 gene. Serum IL-1 levels increased exponentially with time. Secretion of IL-1 from the developed tumors was associated with decreased food consumption, reduced body weight and reduced blood glucose levels. Body composition analysis revealed that IL-1 caused a significant loss in fat tissue without
more » ... tissue without affecting lean body mass and water content. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) activities and mRNAs levels of these enzymes were reduced, and 2-deoxy-glucose (2DG) uptake by peripheral tissues was enhanced. mRNA levels of glucose transporters in the liver were determined by Real Time PCR (RT-PCR) analysis. Glut-3 mRNA levels were up regulated by IL-1 . Glut-1 and glut-4 mRNA levels in IL-1 mice were similar to mRNA levels in pair-fed mice bearing non-secreting tumor. mRNA level of Glut-2, the major glucose transporter of the liver, was down regulated by IL-1 . It is concluded that both decreased glucose production by the liver and enhanced glucose disposal lead to the development of hypoglycemia in mice bearing IL-1 secreting tumor. The observed changes in expression of hepatic glucose transporters that are not dependent on insulin may contribute to the increased glucose uptake.
doi:10.1210/en.2004-0323 pmid:15297440 fatcat:5m5cfeukszehpdjbyyubuiyskm