Understanding age and diabetes related changes in erythrocyte membrane

Abstract

Type 2 Diabetes mellitus (T2DM) is an age-related disease with an inflammatory and oxidative aetiology. Hyperglycaemia significantly contributes to oxidative stress, leading to lipid peroxidation and the formation of advanced glycation or lipoxidation end products (AGEs/ALEs). Evidence indicates that T2DM and ageing affect erythrocyte membrane fluidity, though the mechanisms remain unclear. This project investigated the correlation between membrane fluidity, tension, and phospholipid composition to understand the interactions between membrane properties, oxidative stress, and lipid composition in erythrocytes. Erythrocytes from healthy volunteers were treated in vitro with high glucose levels, with and without glyoxal or methylglyoxal. Membrane fluidity increased with long-term glucose treatment at 100 mM and in the presence of glyoxal at 5 mM and 100 mM glucose, while ageing in 5 mM glucose showed no changes. Membrane tension increased for all participants at 22 mM glucose, but glyoxal and methylglyoxal results were inconsistent. Analysis of intracellular reactive oxygen species (ROS) was inconsistent, but aged cells showed increased phosphatidylserine exposure after 4-hour glucose treatment, which is indicative of changes in the membrane. Liquid chromatography-tandem mass spectrometry revealed erythrocytes aged in physiological glucose levels had increased PC 28:0|PC 14:0_14:0, while higher glucose levels increased unsaturated fatty acyl chains, including PC 34:3, and PE 41:7|PE 19:2_22:5 at 22 mM glucose. The 100 mM glucose treatment showed elevated levels of PE 41:7|PE 19:2_22:5, PE 34:1|PE 16:0_18:1, and PE 34:1|PE 16:0_18:1. PC 28:0|PC 14:0_14:0 and PC 28:0 remained high at 5 mM compared to 22 mM and 100 mM glucose. This increase in the number of double bonds in phospholipids at higher glucose levels likely contributed to the increased membrane fluidity observed at 100 mM glucose. These findings suggest that exposure of erythrocytes to high glucose induces changes in lipid composition, which can significantly affect membrane dynamics. This highlights the complex relationship between glucose levels, ageing, and erythrocyte membrane properties. The small sample size of the study and interindividual variability in oxidative stress markers emphasise the need for further research to elucidate these mechanisms and identify potential therapeutic targets for managing T2DM-related complications.