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FEBS Lett. 2019 Jul;593(13):1598-1615. doi: 10.1002/1873-3468.13495. Epub 2019 Jun 28.

Altered N-glycosylation profiles as potential biomarkers and drug targets in diabetes.

Author information

1
Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia.
2
Genos Glycoscience Research Laboratory, Zagreb, Croatia.

Abstract

N-glycosylation is a ubiquitous protein modification, and N-glycosylation profiles are emerging as both biomarkers and functional effectors in various types of diabetes. Genome-wide association studies identified glycosyltransferase genes as candidate causal genes for type 1 and type 2 diabetes. Studies focused on N-glycosylation changes in type 2 diabetes demonstrated that patients can be distinguished from healthy controls based on N-glycome composition. In addition, individuals at an increased risk of future disease development could be identified based on N-glycome profiles. Moreover, accumulating evidence indicates that N-glycans have a major role in preventing the impairment of glucose-stimulated insulin secretion by maintaining the glucose transporter in proper orientation, indicating that interindividual variation in protein N-glycosylation might be a novel risk factor contributing to diabetes development. Defective N-glycosylation of T cells has been implicated in type 1 diabetes pathogenesis. Furthermore, studies of N-glycan alterations have successfully been used to identify individuals with rare types of diabetes (such as the HNF1A-MODY), and also to evaluate functional significance of novel diabetes-associated mutations. In conclusion, both N-glycans and glycosyltransferases emerge as potential therapeutic targets in diabetes.

KEYWORDS:

HNF1A-MODY; N-glycosylation; glycosyltransferase; type 1 diabetes; type 2 diabetes

PMID:
31215021
DOI:
10.1002/1873-3468.13495

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