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Hyperglycemia and RBCs: too sweet to survive

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Abstract

Sustained untreated hyperglycemia is associated with complications at molecular, cellular, and organ levels in the body that ultimately lead to comorbidities including cardiovascular-related pathologies, neuropathies, nephropathies, blindness, limb amputations, etc. Mature RBCs are unique in their structure and function; being without cellular organelles including nucleus and mitochondria, they are highly sensitive and responsive to the molecular changes in their microenvironment in general and elevated glucose in particular. They lack the ability to synthesize new proteins, replenish its enzyme-based antioxidant machinery, and replace any cellular components in the event of oxidative damage. Although they are dependent on glycolytic processing of glucose for their energy requirements, sustained exposure to hyperglycemia significantly impacts their structure as well as function and leads to early aging of the circulating RBCs with shortened lifespan. Loss of deformability due to hyperglycemia prohibits them to reversibly change their shape and squeeze through the microvasculature, a hallmark of RBC functionality for nutrient and gaseous exchanges. This mini-review of literature signifies the effect of hyperglycemia on RBCs in terms of eryptosis, lipid peroxidation in the cell membrane to compromise membrane integrity which significantly alters its deformity and coaguability, and adherence to endothelial surface leading loss of functionality and life-span.

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Abbreviations

AGEs:

Advanced glycation end products

Arg-P:

Arg-pyrimidine

CEL:

Carboxyethyllysine

CML:

Carboxymethylysine

CP450:

Cytochrome P-450

FAAD:

Fas-associated death domain

FasL:

Fas ligand

GLUT1:

Glucose transporter 1

GLUT4:

Glucose transporter 4

HSCs:

Hematopoietic stem cells

LDH:

Lactate dehydrogenase

MDA:

Malonyldialdehyde

MCV:

Mean corpuscular volume

Na+/K+-ATPase:

Na+/K+ adenosine triphosphatase (ATPase)

ROS:

Reactive oxygen species

RBCs:

Red blood cells

WHO:

World Health Organization

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We thank SRC for supporting this student research project.

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  1. Sulaiman AlRajhi Colleges, PO Box 777, Al Bukairiyah, 51941, AlQaseem, Kingdom of Saudi Arabia

    Ahmad Mamoun Rajab & Khawaja Husnain Haider

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Mamoun Rajab, A., Haider, K.H. Hyperglycemia and RBCs: too sweet to survive. Int J Diabetes Dev Ctries 38, 357–365 (2018). https://doi.org/10.1007/s13410-018-0613-6

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