title: Biological activity studies of the novel glucagon-like peptide-1 derivative HJ07.
abstract: OBJECTIVE
  To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1 (GLP-1) conjugate HJ07.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes.
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li-Dan
authors.initials: LD
authors.lastname: Sun
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: ydhuangwenlong@126.com.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Huang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D003374:Coumarins; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse
keywords: Coumarin-GLP-1 conjugate; Glucagon-like peptide-1; Glucose lowering effect