Tumor growth causes cancer cells to become hypoxic. A hypoxic condition is a hallmark of cancer. Metabolism of cancer cells differs from metabolism of normal cells. Cancer cells prefer the process of glycolysis as a source of ATP. Process of glycolysis generates only two molecules of ATP per one molecule of glucose, whereas the complete oxidative breakdown of one molecule of glucose yields 36 molecules of ATP. Therefore, cancer cells need more molecules of glucose in comparison with normal cells. Increased uptake of glucose by these cells is due to overexpression of glucose transporters, especially GLUT1 and GLUT3, that are hypoxia responsive, as well as other glucose transport proteins. Increased expression of these carrier proteins may be used in anticancer therapy. This phenomenon is used in diagnostic techniques such as FDG-PET. It is also suggested, and there are observations, that therapeutic inhibition of glucose transporters may be a method in treatment of cancer patients. On the other hand, there are described cases, in which upregulation of glucose transporters, as, for example, NIS, which is used in radioiodine therapy, can help patients with cancer. The aim of this review is the presentation of possibilities, and how glucose transporters can be used in anticancer therapy.
Leptin shows pleiotropic effects in organisms including an important role in the regulation of glucose homeostasis. Elevated serum leptin, particularly in obese individuals, is a warning sign of energy imbalance, hyperinsulinemia, insulin resistance and other metabolic risk factors that are strongly associated with type 2 diabetes. Obesity is also related to a higher rate of infections and immune function deterioration may in part ensue from decreased glucose uptake as the main energy source for lymphocytes. The aim of this study was to investigate the effect of physiologic and low pathophysiologic gender-specific leptin concentration found in lean and obese subjects on glucose transport, the expression of glucose transporters and leptin receptors in human peripheral blood lymphocytes. Isolated lymphocytes were incubated with human leptin at gender-specific concentrations observed in normal weight and obese subjects. Glucose uptake in lymphocytes was determined using nonmetabolizable radiolabeled deoxy-d-glucose. The expression of GLUT1, 3, 4 and leptin receptors was investigated using methods of immunocytochemistry and flow cytometry. Leptin at concentrations used in the study does not change glucose transport into lymphocytes and seems to have no influence on the expression of glucose transporters and leptin receptors. Further studies are necessary to address the relationship between leptin, glucose transport and the lymphocytes’ function in obesity.
Polycystic ovary syndrome (PCOS) is linked to increased risk of insulin resistance and diabetes mellitus in patients’ later life. The aim of this study was to investigate uptake of deoxy-d-glucose by peripheral blood lymphocytes of PCOS patients with normal fasting plasma glucose and normal glucose tolerance test. The study involved 20 patients with PCOS with normal fasting plasma glucose and normal glucose in 60 and 120 min of oral glucose tolerance test, aged 18–32 (mean 23), BMI between 20 and 30 (mean 26). A control group consisted of 20 healthy women matched for glucose level (normoglycemia), aged 18–28 years (mean 23), BMI 20–25 (mean 23). Blood for the studies was collected in fasting conditions onto heparin. Lymphocytes were isolated within 2 h from collection by centrifuging. The intracellular transport into lymphocytes was studied using tritium-labeled deoxy-d-glucose and measured with a liquid scintillation counter. Radioactivity in curie per minute (cpm) was evaluated after 24 h. An initial examination was performed to check the presence of GLUT4 in peripheral blood lymphocytes of PCOS women. In all of the studied time points, the value of cpm for lymphocytes of PCOS patients was statistically significantly lower in comparison with the value obtained for lymphocytes of healthy women. However, the profile of deoxy-d-glucose uptake (d cpm) was the same for lymphocytes in both studied groups without statistically significant differences. In lymphocytes of PCOS patients, GLUT4 was detected. The obtained results indicate that PCOS affects the intracellular transport of deoxy-d-glucose into lymphocytes of PCOS patients with normal glucose level.
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