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Eur J Pharmacol. 2015 Nov 15;767:211-9. doi: 10.1016/j.ejphar.2015.10.028. Epub 2015 Oct 22.

Coumaglutide, a novel long-acting GLP-1 analog, inhibits β-cell apoptosis in vitro and invokes sustained glycemic control in vivo.

Author information

1
Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
2
Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, China.
3
Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: ydhuangwenlong@126.com.
4
Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: qianhai24@163.com.

Abstract

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 (t1/2=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 β-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 μM 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 A1c (HbA1C), 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 β-cell from apoptosis in vitro and induce a durable restoration of glycemic control (normalization of both HbA1C 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.

KEYWORDS:

Apoptosis; Coumaglutide; Glycemic control

PMID:
26481165
DOI:
10.1016/j.ejphar.2015.10.028
[Indexed for MEDLINE]

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