Analysis of N-glycan in serum glycoproteins from db/db mice and humans with type 2 diabetes.
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 alpha1,6-fucose in the serum of db/db mice. The level of alpha1,6-fucosyltransferase mRNA was increased in the liver of the db/db mice. The ratio of a biantennary N-glycan with alpha1,6-fucose to that without alpha1,6-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 alpha1,6-fucose with a bisecting N-acetylglucosamine. In conclusion, the increase in alpha1,6-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 alpha1,6-fucosyltransferase mRNA level in the liver. The increased alpha1,6-fucosylation may affect protein properties associated with the pathophysiology of type 2 diabetes.
First Dept. of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
Naofumi
N
Itoh
Shinji
S
Sakaue
Hiroaki
H
Nakagawa
Masaki
M
Kurogochi
Hiroshi
H
Ohira
Kisaburo
K
Deguchi
Shin-Ichiro
S
Nishimura
Masaharu
M
Nishimura
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis*
D006023:Glycoproteins; D011134:Polysaccharides; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase