title: Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models.
abstract: OBJECTIVE
  Dipeptidyl deptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents. The purpose of this study was to assess the acute and chronic effects of SHR117887, a novel DPP-4 inhibitor, on metabolic control and pancreatic β-cell function in normal or diabetic rodent models.
  
  
  METHODS
  In the acute experiments, ICR mice, diet-induced obese (DIO) rats and ob/ob mice were subjected to an oral glucose tolerance test (OGTT) following a single oral administration of SHR117887 (0.1, 0.3, 1 or 3 mg/kg). Blood samples were collected to measure glucose, insulin, DPP-4 activity and active GLP-1 level. In the chronic experiments, ob/ob mice was administered SHR117887 (3, 10 or 30 mg/kg) twice daily for 33 d to assess the effects on metabolic control and pancreatic β-cell function. Vildagliptin (LAF237) was used as a positive control in all the experiments.
  
  
  RESULTS
  Acute oral administration of SHR117887 dose-dependently decreased the serum DPP-4 activity and improved glucose tolerance in ICR mice, DIO rats and ob/ob mice. This was accompanied by significant increases in the serum active GLP-1 and insulin levels. Chronic administration of SHR117887 significantly decreased fasting blood glucose level and improved the lipid profiles in ob/ob mice by reducing the serum triglyceride and free fatty acid levels, and its efficacy was comparable with that of vildagliptin at the same molarity. Moreover, chronic administration of SHR117887 increased the insulin staining of islet cells, which is suggestive of improved β-cell function.
  
  
  CONCLUSIONS
  SHR117887 is a potent DPP-4 inhibitor that improves metabolic control and β-cell function in diabetic rodent models, suggesting that it could be a new therapeutic agent for the treatment of type 2 diabetes.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Xiao
authors: X
authors: Liu
authors: Li-na
authors: LN
authors: Zhang
authors: Ying
authors: Y
authors: Feng
authors: Lei
authors: L
authors: Zhang
authors: Hui
authors: H
authors: Qu
authors: Guo-qing
authors: GQ
authors: Cao
authors: Ying
authors: Y
authors: Leng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008820:Mice, Obese; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents