The role of phosphate transporters in the development of glomerular clacification and in the induction of insulin resistance in podocytes ; Rola transporterów fosforanowych w rozwoju kłębuszkowej kalcyfikacji oraz w indukcji insulinooporności podocytów

Podocytes are specialized cells of the visceral epithelium, which, together with the glomerular capillary endothelium and the basement membrane, form a unique structure – the glomerular filtration barrier (GFB). In the morphology of the podocyte, foot processes can be distinguished, which, by interlocking with each other, form slit diaphragms (SD) – highly dynamic, and thus the most sensitive to damage, elements of the GFB. It is SD that prevents macromolecules from entering the ultrafiltrate. Podocytes are also insulin sensitive, and alterations in the homeostasis of this hormone affect their physiology. Diabetic kidney disease (DKD), is an example of the most common disorder leading to podocyte injury. Chronic hyperinsulinemia and hyperglycemia present in the course of DKD cause insulin resistance of podocytes and progressive disintegration of GFB, which leads to albuminuria. GFB damage is often overlooked in the initial stages of the disease due to its oligosymptomatic manifestation. Soft tissues calcification is a deleterious complication of diabetes. Due to dysregulated hormonal balance and abnormal kidney function, phosphate ions (Pi) are retained in the body. Long-lasting hyperphosphatemia favors the deposition of calcium phosphate salts in organs where this process does not occur under physiological conditions. So far, scientists have most accurately described the pathomechanism of vascular calcification (VC). From these studies it is known that mechanism of VC involves the significant participation of sodium-dependent phosphate transporters (NaPi 2c, Pit 1, Pit 2), whose function is the transport of Pi into the cell, and the XPR1, which exports Pi from the cell. Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) also participates in maintaining phosphate homeostasis, mainly by generation of pyrophosphate (PPi) – the strongest inhibitor of calcification. Both NPP1 and Pit 1 are also regulators of intracellular insulin signaling. The aim of the research was to determine the influence of the diabetic ...