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Am J Physiol Endocrinol Metab 293: E1069-E1077, 2007. First published July 31, 2007; doi:10.1152/ajpendo.00182.2007
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Analysis of N-glycan in serum glycoproteins from db/db mice and humans with type 2 diabetes

Naofumi Itoh,1 Shinji Sakaue,1 Hiroaki Nakagawa,2 Masaki Kurogochi,2 Hiroshi Ohira,1 Kisaburo Deguchi,2 Shin-Ichiro Nishimura,2 and Masaharu Nishimura1

1First Department of Medicine, Graduate School of Medicine; and 2Graduate School of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan

Submitted 22 March 2007 ; accepted in final form 19 July 2007

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.

{alpha}1,6-fucosylation; {alpha}1,6-fucosyltransferase; liver



Address for reprint requests and other correspondence: S. Sakaue, First Dept. of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan (e-mail: sakaue-s{at}med.hokudai.ac.jp)







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