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- W2969428497 abstract "Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1–39)-NH2, Cys40-Exenatide (1–39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1–39)-NH2 and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1–39)-NH2 were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugation C2 was selected for further investigation. Glucoregulatory and insulin secretion assay and hypoglycemic duration test were accessed and showed that C2 was capable of comparable insulinotropic activities and glucose-lowering abilities with those of liraglutide and exenatide. Cell protective effects in INS-1 cells confirmed that C2 had relatively protection effects. Meanwhile, once daily injection of C2 to STZ-induced diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. Acute feeding studies were evaluated in DIO mice. These results suggested that C2 is a promising agent for further investigation of its potential to treat diabetes patients with obese." @default.
- W2969428497 created "2019-08-29" @default.
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- W2969428497 date "2019-10-01" @default.
- W2969428497 modified "2023-10-15" @default.
- W2969428497 title "Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties" @default.
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- W2969428497 doi "https://doi.org/10.1016/j.bmc.2019.115070" @default.
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