IN-VIVO EFFECTS OF INSULIN ON TUMOR AND SKELETAL-MUSCLE GLUCOSE-METABOLISM IN PATIENTS WITH LYMPHOMA

Background. The anabolic properties of insulin have been suggested for use to reverse malnutrition associated with cancer. The host and tumor sensitivities to insulin are critical for such treatments, which aim to improve patient nutrition. The authors studied insulin effects on tumor and skeletal muscle metabolism with 2-[F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) and positron emission tomography (PET). Methods. Six patients with lymphoma twice underwent [F-18]FDG-PET imaging: once after fasting overnight and once during euglycemic hyperinsulinemic clamp. The dynamic uptake of the glucose analogue [F-18]FDG was measured in diseased nodes and upper arm skeletal muscle in both metabolic states. The [F-18]FDG uptake in muscle and the whole body glucose use during euglycemic hyperinsulinemic clamp were compared with those of weight-matched healthy subjects studied under similar circumstances. Results. In lymphomatous tissue, [F-18]FDG uptake rates were similar in overnight fasting and euglycemic hyperinsulinemic clamp (38 +/- 10 versus 41 +/- 9 mu mol/100 g/minute, not significant), whereas glucose uptake in skeletal muscle was increased by insulin (1.7 +/- 0.2 versus 3.8 +/- 0.5 mu mol/100g/minute, P = 0.012). Both basal(2.3 +/- 0.2 mu mol/100 g/minute, P = 0.061) and insulin-stimulated (8.5 +/- 1.9 mu mol/100 g/minute, P = 0.055) skeletal arm muscle glucose uptake rates were higher in control subjects than in patients. Whole body glucose use was 55% lower in patients than in control subjects (17 +/- 3 mu mol/ kg/minute versus 38 +/- 3 mu mol/kg/minute, P = 0.002), consistent with insulin resistance in cancer. Conclusions. We found that insulin does not induce major changes in glucose uptake of lymphomatous tissue. Although insulin sensitivity of skeletal muscle was also reduced in patients with lymphoma, the net insulin effect may counteract imbalance between glucose uptake of tumor and muscle, offering a potential means to circumvent at least some metabolic abnormalities found in cancer.