Coumaglutide, a novel long-acting GLP-1 analog, inhibits β-cell apoptosis in vitro and invokes sustained glycemic control in vivo.
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.
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.
Lidan
L
Sun
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.
Chuandong
C
Wang
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.
Yuxuan
Y
Dai
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.
Yingying
Y
Chu
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.
Jing
J
Han
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.
Jie
J
Zhou
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.
Xingguang
X
Cai
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.
Wenlong
W
Huang
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.
Hai
H
Qian
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival; D003374:Coumarins / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004435:Eating / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010179:Pancreas / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D000925:Anticoagulants; D001786:Blood Glucose; D003374:Coumarins; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D020011:Protective Agents; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000611308:coumaglutide
Apoptosis; Coumaglutide; Glycemic control