Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor-alpha expression in skeletal muscle

The roles of tumor necrosis factor (TNF)-alpha and the facilitative glucose transporter (GLUT) 4 on the induction of insulin resistance in peripheral tissues of cancer patients was examined by quantitative competitive PCR on biopsies of abdominal rectal muscle from patients with gastrointestinal can cer. The degree of insulin resistance in these patients was measured by the euglycemic hyperinsulinemic glucose clamp using a high physiologic insulin concentration (100 mu U/ml). Quantitative competitive PCR was carried out using DNA competitors constructed by deleting 20-30 bp between the two prim er annealing sites. Decreased glucose uptake (M value) in peripheral tissue s was accompanied by a significantly increased TNF-alpha mRNA in skeletal m uscle (r = 0.867, p = 0.0025), GLUT4 mRNA, however, was positively correlat ed with M values (r = 0.739, p = 0.015). The amounts of mRNAs for TNF-alpha and GLUT4 in skeletal muscle were not correlated. Serum TNF-alpha concentr ations remained below the limit of detection. These findings suggest that t he insulin resistance in peripheral tissues of cancer patients is in part d ue to the induction TNF-alpha mRNA and the down regulation of GLUT4 mRNA in peripheral tissues. (C) 1998 Academic Press.