Глюкозні транспортери сімейства GLUT у патогенезі проліферативної діабетичної ретинопатії пацієнтів із цукровим діабетом 2-го типу

Abstract

The supply of glucose to neurons of the brain and retina is carried out by a specific, facilitated transport with the participation of sodium-independent glucose transporters of the GLUT family. Studying the mechanisms of glucose transport with pharmacological or genetic inhibition of transporters is considered as a promising way to reduce glucose-toxic damage to the retina to prevent diabetic retinopathy. We studied the content of GLUT1, GLUT3, GLUT4 and Hypoxia inducible factor 1 alpha (HIF-1α) in the plasma of patients with different stages of proliferative diabetic retinopathy (PDR), duration of type 2 diabetes (T2D) was up to 20 and over 20 years, and control group. Research on the level of transporters in the blood plasma was carried out by the method of immuno-enzymatic analysis using Elabscience kits (USA). No significant difference in the GLUT1 and GLUT4 blood plasma content was found between patients with PDR and control individuals, and the GLUT3 content was 2-fold higher. Also, the content of HIF-1α was 25% higher. No significant fluctuations in the content of transporters GLUT1, GLUT3, GLUT4, HIF-1α were found depending on the duration of T2DM, the degree of deepening of PDR and the level of hyperglycemia. Correlation analysis revealed a significant two-way correlation of the GLUT3 index with blood glucose level (r = 0.581), HbA1C (r = 0.553), GLUT1 (r = 0.440) and GLUT4 (r = 0.372). The conservatism of GLUT1 transporter content in the studied groups gives a reason to consider protein expression as genetically determined for the basic maintenance of homeostasis. The GLUT3 content increase in patients with PDR, which does not depend on the retinal damage degree, duration of T2D and glucose concentration, defines this mechanism of transport as the main pathogenetic link of glucose toxicity in neurons against the background of chronic hyperglycemia. Insulin-dependent transporter GLUT4 is probably not involved in the occurrence of PDR under of T2D.