Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 767, Issue -, Pages 211-219Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.10.028
Keywords
Coumaglutide; Apoptosis; Glycemic control
Categories
Funding
- Natural Science Foundation of Jiangsu Province [BK2012356]
- National Natural Science Foundation of China [81172932, 81273376]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGZ201103]
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Glucagon-like peptide-1 (GLP-1) is a potential candidate for the treatment of type 2 diabetes. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t112=2 min). Our recent discovery of the novel long-acting GLP-1 analog, coumaglutide, elicits favorable hypoglycemic effects. The present study was aimed at determining the protection effect of 13-cell from apoptosis and in vivo pharmacologic properties of coumaglutide in diabetic mice. To determine the protective effect of coumaglutide on INS-1 cell viability and apoptosis, cells were exposed to 1 ttM streptozotocin (STZ) and coumaglutide for 24 h. Moreover, STZ-induced diabetic mice were treated daily with coumaglutide for 20 days and a range of pharmacologic parameters, including hemoglobin Al c (HbAlC), intraperitoneal glucose tolerance, food intake and body weight were assessed before and after the treatment. As with other glucagon-like peptide-1 receptor agonizts, coumaglutide was able to protect 13-cell from apoptosis in vitro and induce a durable restoration of glycemic control (normalization of both HbAlC and improvement of intraperitoneal glucose tolerance) in diabetic mice. It can be concluded that coumaglutide retains native GLP-1 activities and thus may serve as a promising hypoglycemic drug candidate. (C) 2015 Elsevier BY. All rights reserved.
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