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

Edit Szabó,Anikó Somogyi,Judit Cserepes,György Várady,Balázs Sarkadi,Botond Literáti-Nagy,Anna Kulin,László Korányi

doi:10.1038/s41598-021-82417-8

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.

Highlights

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
When studying red blood cells (RBC) membrane proteins in the multifactorial Alzheimer’s disease (AD), we found that the levels of GLUT1, INSR, ABCA1 and ABCG2 proteins were significantly reduced in late
When measuring the RBC expression of the ABCG2 protein we did not observe a difference between control individuals and T2DM patients. It has been shown earlier, that the common polymorphism Q141K in ABCG2, causes lower RBC protein expression[3,6], we examined the potential effect of this polymorphism in T2DM patients

Summary

Introduction

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. 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. Environmental and nutritional factors greatly influence the actual phenotypic effects of the genetic polymorphisms In this project we initiated a new approach to provide potential biomarkers for tracking disease progression and predicting possible complications in T2DM, by studying the diabetes-related transporters in the membranes of the red blood cells (RBC).

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Conclusion