期刊
JOURNAL OF ENDOCRINOLOGY
卷 248, 期 2, 页码 145-154出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-20-0255
关键词
GLP-1; supaglutide; diabetes; glucose homeostasis; obesity
资金
- Ministry of Science and Technology [2011ZX09102, 2017ZX09303001]
- Shanghai Science and Technology Department [2017ZX09303001]
- Yunnan Provincial Science and Technology Department, Yunnan Development and Reform Commission, Kunming Municipal Bureau of Human Resources and Social Security
Supaglutide, a novel GLP-1 mimetic, demonstrated significant hypoglycemic and beta-cell trophic effects in diabetic rhesus monkeys, helping to regulate blood glucose and lipid homeostasis.
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 beta-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 revealt hat supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.
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