title: A mutated glucagon-like peptide-1 with improved glucose-lowering activity in diabetic mice.
abstract: OBJECTIVE
  The aim of this study was to characterize the conformation and potency of a mutated glucagon-like peptide-1 (mGLP-1), and evaluate its glucose-lowering activity in diabetic mice.
  
  
  METHODS
  Spectroscopy techniques were employed to characterize the conformation of mGLP-1. Glucose tolerance test was performed to determine the potency of mGLP-1 in vivo. A mouse model in which diabetes was induced by multiple low doses of streptozotocin was established to evaluate the glucose-lowering activity of mGLP-1.
  
  
  RESULTS
  Compared with native GLP-1, mGLP-1 had a similar conformation and an enhanced potency in vivo. In diabetic mice, mGLP-1 displayed a significantly improved glucose-lowering activity as judged by fasting glucose and insulin, oral glucose tolerance test, beta cell function analysis and histochemical analysis.
  
  
  CONCLUSIONS
  Collectively, mGLP-1 possesses an improved glucose-lowering activity in vivo and therefore can be recognized as a potential candidate for the future development of anti-diabetic drugs.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.forename: Yue
authors.initials: Y
authors.lastname: Tong
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
authors.forename: Wenbing
authors.initials: W
authors.lastname: Yao
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015195:Drug Design; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D050505:Mutant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D050505:Mutant Proteins; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1