Altered N‐glycosylation profiles as potential biomarkers and drug targets in diabetes. Issue 13 (28th June 2019)

• Record Type: Journal Article
• Authors: Rudman, Najda; Gornik, Olga; Lauc, Gordan
• Is Part Of: FEBS letters. Volume 593:Issue 13(2019)
• Page Start: 1598
• Page End: 1615
• Publication Date: 2019-06-28
• Subjects: glycosyltransferase -- HNF1A‐MODY -- N‐glycosylation -- type 1 diabetes -- type 2 diabetes; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13495
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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.