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• W2013173650 abstract "Improved glucagon-like peptide-1 (GLP-1) receptor activation is considered one of the most effective targets for antidiabetic therapy. For this purpose, we modified the GLP-1 analog of exendin-4 using two fatty acids (FA) either lauric acid (LUA, C12) or palmitic acid (PAA, C16) at its two lysine residues, to produce; Lys12-FA-Exendin-4 (FA-M2), Lys27-FA-Exendin-4 (FA-M1), or Lys12,27-diBA-Exendin-4 (FA-Di). The structural, biological, and pharmaceutical characteristics of these exendin-4 analogs were then investigated. Biological activity tests demonstrated that LUA-M1 had well-preserved in vivo antidiabetic activity and in vitro insulinotropic activity with minimum GLP-1 receptor binding affinity loss as compared with exendin-4. Furthermore, pharmacokinetic studies in rats revealed that s.c. administration of LUA-M1 significantly enhanced pharmacokinetic parameters, such as, elimination half-life, mean residence time, and AUC values as compared with exendin-4. The protracted antidiabetic effects of LUA-M1 were also confirmed by prolonged normoglycemia observed in type 2 diabetic mice (20 nmol/mouse single injection of exendin-4 or LUA-M1 induced normoglycemia for 6 or 24 h, respectively). These findings suggest that FA conjugated exendin-4s should be considered potential candidates for the treatment of diabetes." @default.
• W2013173650 created "2016-06-24" @default.
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• W2013173650 date "2010-05-01" @default.
• W2013173650 modified "2023-09-26" @default.
• W2013173650 title "The fatty acid conjugated exendin-4 analogs for type 2 antidiabetic therapeutics" @default.
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• W2013173650 doi "https://doi.org/10.1016/j.jconrel.2010.01.024" @default.
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