摘要: AIM:To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1(GLP-1) conjugate HJ07.METHOD:A receptor activation experiment was performed in HEK 293 cells and the glucose lowering ability was evaluated with hypoglycemic duration and glucose stabilizing tests.Chronic treatment was performed by daily injection of exendin-4,saline,and HJ07.Body weight and HbA1c were measured every week,and an intraperitoneal glucose tolerance test was performed before treatment and after treatment.RESULTS:HJ07 showed well-preserved receptor activation efficacy.The hypoglycemic duration test showed that HJ07 possessed a long-acting,glucose-lowering effect and the glucose stabilizing test showed that the antihyperglycemic activity of HJ07 was still evident at a predetermined time(12 h) prior to the glucose challenge(0 h).The long time glucose-lowering effect of HJ07 was better than native GLP-1 and exendin-4.Furthermore,once daily injection of HJ07 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance.CONCLUSION:The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes.