Alterations in erythrocyte membrane transporter expression levels in type 2 diabetic patients

Abstract

Type 2 diabetes mellitus (T2DM) is one of the most common multifactorial diseases and several membrane transporters are involved in its development, complications and treatment. We have recently developed a flow-cytometry assay panel for the quantitative determination of red cell membrane protein levels with potential relevance in diseases. Here we report a detailed phenotypic analysis of a medium scale, clinically based study on the expression of T2DM-related membrane proteins, the GLUT1, GLUT3, MCT1, URAT1, ABCA1, ABCG2 and the PMCA4 transporters in erythrocytes. By comparing age-matched control subjects and three groups of T2DM patients (recently diagnosed, successfully managed, and patients with disease-related complications), we found significant differences in the membrane expression levels of the transporters in these groups. This is a first detailed analysis of T2DM related alterations in erythrocyte membrane transporter protein levels, and the results suggest significant changes in some of the transporter expression levels in various patient groups. By performing a further, more detailed analysis of the clinical and molecular biology parameters, these data may serve as a basis of establishing new, personalized diagnostic markers helping the prevention and treatment of type 2 diabetes.

Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring

“…As suggested many years ago, UA potentially enters RBCs by glycolysis-dependent and ATP-activated facilitated transport [ 51 , 52 ] through membrane transporters, such as URAT1 and ABCG2 [ 53 ]. UA transport seems to be accelerated with decreasing pH [ 52 ].…”

Genetic Modulation of the GLUT1 Transporter Expression—Potential Relevance in Complex Diseases

“…The expression level of the RBC membrane proteins was measured by a method developed by our research group (for details, see refs [ 10 , 23 ]). The RBC membranes were fixed with 1% formaldehyde solution and the resulting RBC membranes (ghosts) were labeled by Alexa Fluor 647 (AF647) conjugated wheat germ agglutinin (WGA-AF647, Thermo Fischer Scientific, Waltham, MA, USA, W32466).…”

Potential role of the ABCG2-Q141K polymorphism in type 2 diabetes

“…This treatment was supplemented in some cases with oral antidiabetics and also with allopurinol (milurit), to reduce uric acid levels. More detailed laboratory and treatment data for the patients examined here are available in ref [ 19 ].…”

“… We have measured the expression levels of ABCG2 in the RBC membranes of normal healthy individuals and T2DM patients. The methods see in ref [ 19 ]. In brief, the fixed and permeabilized RBC membranes (ghosts) were incubated with the Bxp34 monoclonal primer antibody (Abcam, cat.…”