Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys

葡萄糖稳态 内科学 内分泌学 二肽基肽酶-4 果糖胺 医学 糖尿病 胰岛素 胰高血糖素样肽-1 胰高血糖素 平衡 胰岛素抵抗 2型糖尿病
作者
Qiaoli Cui,Yijing Liao,Yaojing Jiang,Xiaohang Huang,Weihong Tao,Quan-Quan Zhou,Anwen Shao,Ying Zhao,Jia Li,Anran Ma,Zhihong Wang,Li Zhang,Zunyuan Yang,Yinan Liang,Minglin Wu,Zhenyan Yang,Wen Zeng,Qinghua Wang
出处
期刊:Journal of Endocrinology [Bioscientifica]
卷期号:248 (2): 145-154 被引量:3
标识
DOI:10.1530/joe-20-0255
摘要

Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t 1/2 < 2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and β-cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide’s therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-week intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.
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