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Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid
- Source :
- EBioMedicine, Vol 2, Iss 11, Pp 1735-1750 (2015), EBioMedicine
- Publication Year :
- 2015
- Publisher :
- Elsevier, 2015.
-
Abstract
- Strategies to prevent diabetic microvascular angiopathy focus on the vascular endothelium. Because red blood cells (RBCs) are less deformable in diabetes, we explored an original concept linking decreased RBC deformability to RBC ascorbate and hyperglycemia. We characterized ascorbate concentrations from human and mouse RBCs and plasma, and showed an inverse relationship between RBC ascorbate concentrations and deformability, measured by osmotic fragility. RBCs from ascorbate deficient mice were osmotically sensitive, appeared as spherocytes, and had decreased β-spectrin. These aberrancies reversed with ascorbate repletion in vivo. Under physiologic conditions, only ascorbate's oxidation product dehydroascorbic acid (DHA), a substrate for facilitated glucose transporters, was transported into mouse and human RBCs, with immediate intracellular reduction to ascorbate. In vitro, glucose inhibited entry of physiologic concentrations of dehydroascorbic acid into mouse and human RBCs. In vivo, plasma glucose concentrations in normal and diabetic mice and humans were inversely related to respective RBC ascorbate concentrations, as was osmotic fragility. Human RBC β-spectrin declined as diabetes worsened. Taken together, hyperglycemia in diabetes produced lower RBC ascorbate with increased RBC rigidity, a candidate to drive microvascular angiopathy. Because glucose transporter expression, DHA transport, and its inhibition by glucose differed for mouse versus human RBCs, human experimentation is indicated.
- Subjects :
- Male
Erythrocytes
Glucose Transport Proteins, Facilitative
DHA, dehydroascorbic acid
Gene Expression
lcsh:Medicine
3-O-Methylglucose
Ascorbic Acid
Mice
chemistry.chemical_compound
Glucose Transport
WT, wildtype mouse
Red Blood Cells
Biomass
GLUT, facilitated glucose transporter
Vitamin A
SVCT, sodium-dependent vitamin C transporter
Mice, Knockout
lcsh:R5-920
Sewage
Vitamin A Deficiency
Polyhydroxyalkanoates
Cell Cycle
Diabetes
β-Spectrin
Erythrocyte fragility
hemic and immune systems
General Medicine
Dehydroascorbic Acid
3. Good health
medicine.anatomical_structure
Dehydroascorbic acid
lcsh:Medicine (General)
Research Article
circulatory and respiratory physiology
3-O-MG, 3-O-methylglucose
medicine.medical_specialty
Biology
RIPA, Western blot cell lysis buffer
General Biochemistry, Genetics and Molecular Biology
Diabetes Mellitus, Experimental
PBS, phosphate buffered saline
Internal medicine
Diabetes mellitus
Diabetes Mellitus
medicine
Animals
Humans
Gulo-/-, gulonolactone oxidase knockout mouse unable to synthesize ascorbate
Obesity
Bacteria
Vitamin C
lcsh:R
Glucose transporter
Biological Transport
TCEP, Tris(2-carboxyethyl)phosphine
medicine.disease
Ascorbic acid
United Kingdom
Osmotic Fragility
Red blood cell
Glucose
Endocrinology
Diabetes Mellitus, Type 2
chemistry
Starvation
Commentary
RBCs, red blood cells
AA, ascorbic acid
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 2
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....16eddbe35ff832798a31c27360b5bdf9