期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 293, 期 4, 页码 E1069-E1077出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00182.2007
关键词
alpha 1,6-fucosylation; alpha 1,6-fucosyltransferase; liver
Glycosylation has an important role in regulating properties of proteins and is associated with many diseases. To examine the alteration of serum N-glycans in type 2 diabetes, we used the db/db mouse model. Serum N-glycans were fluorescence labeled and applied to HPLC. There were reproducible differences in N-glycan profiles between the db/db mouse model and the db/+ control. The structures of the oligosaccharides, which had changed in their amounts, were analyzed by a two-dimensional mapping method, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, and exoglycosidase digestion. Those analyses revealed an increase in the N-glycans possessing alpha 1,6-fucose in the serum of db/db mice. The level of alpha 1,6-fucosyltransferase mRNA was increased in the liver of the db/db mice. The ratio of a biantennary N-glycan with alpha 1,6-fucose to that without alpha 1,6-fucose in the liver tissue of the db/db mouse was increased relative to the db/+ control. Next, we analyzed the serum N-glycan profile in human subjects with type 2 diabetes and found an increased amount of a biantennary N-glycan that had an alpha 1,6-fucose with a bisecting N-acetylglucosamine. In conclusion, the increase in alpha 1,6-fucosylation is a striking change in the serum N-glycans of the db/db mice, whereas the change in the fucosylation in humans with type 2 diabetes was small, albeit statistically significant. It is likely that the change is caused, at least partially, by the increase in the alpha 1,6- fucosyltransferase mRNA level in the liver. The increased alpha 1,6-fucosylation may affect protein properties associated with the pathophysiology of type 2 diabetes.
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