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- Title
Increased Expression of β-N-Acetylglucosaminidase in Erythrocytes From Individuals With Pre-diabetes and Diabetes.
- Authors
Park, Kyoungsook; Saudek, Christopher D.; Hart, Gerald W.
- Abstract
OBJECTIVE--O-linked β-N-acetylglucosamine (O-GlcNAc) plays an important role in the development of insulin resistance and glucose toxicity. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT), which attaches O-GlcNAc to serine and/or threonine residues of proteins and by O-GlcNAcase, which removes O-GlcNAc. We investigated the expression of these two enzymes in erythrocytes of human subjects with diabetes or pre-diabetes. RESEARCH DESIGN AND METHODS--Volunteers with norreal condition, pre-diabetes, and diabetes were recruited through a National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) study and at the Johns Hopkins Comprehensive Diabetes Center. Erythrocyte proteins were extracted and hemoglobins were depleted. Global O-GlcNAcylation of erythrocyte proteins was confirmed by Western blotting using an O-GlcNAc-specific antibody. Relative OGT and O-GlcNAcase protein amounts were determined by Western blot analysis. Relative expression of O-GlcNAcase was compared with the level of A1C. RESULTS--Erythrocyte proteins are highly O-GlcNAcylated. O-GlcNAcase expression is significantly increased in erythrocytes from both individuals with pre-diabetes and diabetes compared with normal control subjects. Unlike O-GlcNAcase, protein levels of OGT did not show significant changes. CONCLUSIONS--O-GlcNAcase expression is increased in erythrocytes from both individuals with pre-diabetes and individuals with less well-controlled diabetes. These findings, together with the previous study that demonstrated the increased site-specific O-GlcNAcylation of certain erythrocyte proteins, suggest that the upregulation of O-GlcNAcase might be an adaptive response to hyperglycemia-induced increases in O-GlcNAcylation, which are likely deleterious to erythrocyte functions. In any case, the early and substantial upregulation of O-GlcNAcase in individuals with pre-diabetes may eventually have diagnostic utility. Diabetes 59:1845-1850, 2010
- Subjects
ERYTHROCYTES; GLUCOSE; INSULIN resistance; PREDIABETIC state; ACYLATION
- Publication
Diabetes, 2010, Vol 59, Issue 7, p1845
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db09-1086