Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2018

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Alexis Guerin-Dubourg
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Résumé

The long-acting glucagon-like peptide-1 analogue liraglutide has proven efficiency in the management of type 2 diabetes and also has beneficial effects on cardiovascular diseases. Liraglutide's protracted action highly depends on its capacity to bind to albumin via its palmitic acid part. However, in diabetes, albumin can undergo glycation, resulting in impaired drug binding. Our objective in this study was to assess the impact of human serum albumin (HSA) glycation on liraglutide affinity. Using fluorine labeling of the drug and 19F NMR, we determined HSA affinity for liraglutide in two glycated albumin models. We either glycated HSA in vitro by incubation with glucose (G25- or G100-HSA) or methylglyoxal (MGO-HSA) or purified in vivo glycated HSA from the plasma of diabetic patients with poor glycemic control. Nonglycated commercial HSA (G0-HSA) and HSA purified from plasma of healthy individuals served as controls. We found that glycation decreases affinity for liraglutide by 7-fold for G100-HSA and by 5-fold for MGO-HSA compared with G0-HSA. A similarly reduced affinity was observed for HSA purified from diabetic individuals compared with HSA from healthy individuals. Our results reveal that glycation significantly impairs HSA affinity to liraglutide and confirm that glycation contributes to liraglutide's variable therapeutic efficiency, depending on diabetes stage. Because diabetes is a progressive disease, the effect of glycated albumin on liraglutide affinity found here is important to consider when diabetes is managed with this drug.

Dates et versions

hal-04468913 , version 1 (20-02-2024)

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Angélique Gajahi Soudahome, Aurélie Catan, Pierre Giraud, Sandrine Assouan Kouao, Alexis Guerin-Dubourg, et al.. Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide. Journal of Biological Chemistry, 2018, 293 (13), pp.4778-4791. ⟨10.1074/jbc.M117.815274⟩. ⟨hal-04468913⟩
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