title: Pharmacological stimulation of serotonin 5-HT1B receptors enhances increases in plasma active glucagon-like peptide-1 levels induced by dipeptidyl peptidase-4 inhibition independently of feeding in mice.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1), an incretin hormone, is released from intestinal L cells in response to nutrient ingestion. Dipeptidyl peptidase-4 (DPP-4) rapidly degrades the active form of GLP-1 to an inactive form in the bloodstream. The present study aimed to investigate the role of serotonin (5-HT)1B receptors in the regulation of plasma active GLP-1 levels and glucose tolerance under DPP-4 inhibition.
  
  
  METHODS
  C57BL6J mice treated with or without alogliptin, a highly selective DPP-4 inhibitor, for 4 days were intraperitoneally injected with either saline, the 5-HT1B/2C receptor agonist meta-chlorophenylpiperazine (mCPP) at 2.5mg/kg and 5mg/kg or the selective 5-HT1B receptor agonist CP94253 at 2.5mg/kg and 5mg/kg, and food-deprived after treatment. An hour later, plasma active GLP-1 levels were determined. Also, a glucose tolerance test was done by injecting D-glucose (2g/kg) following the injection of saline or CP94253 (5mg/kg) in mice treated with alogliptin.
  
  
  RESULTS
  Intraperitoneal injection of mCPP (2.5 and 5mg/kg) or CP94253 (2.5 and 5mg/kg) in mice treated with alogliptin for 4 days significantly increased plasma active GLP-1 levels compared with saline controls in mice that were food-deprived after the injections. While intraperitoneal injection of either mCPP or CP94253 alone had no significant effect on plasma active GLP-1 levels, the injection of CP94253 improved glucose tolerance in mice treated with alogliptin compared with saline.
  
  
  CONCLUSIONS
  These findings suggest that pharmacological stimulation of 5-HT1B receptors enhances the increases in plasma active GLP-1 induced by DPP-4 inhibition independently of feeding and also improves glucose tolerance in mice.
authors.affiliation: Department of Diabetes Technology, Tohoku University Graduate School of Biomedical Engineering, 6-6-11 Aramakiaza-Aoba, Aoba-ku, Sendai, Miyagi 980, Japan. Electronic address: katsu@trc.med.tohoku.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Nonogaki
authors.affiliation: Department of Diabetes Technology, Tohoku University Graduate School of Biomedical Engineering, 6-6-11 Aramakiaza-Aoba, Aoba-ku, Sendai, Miyagi 980, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D018565:Food-Drug Interactions; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000819:agonists / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D044302:Receptor, Serotonin, 5-HT1B / Q000737:chemistry / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C097067:CP 94253; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000603631:HTR1B protein, mouse; D007328:Insulin; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D014498:Uracil; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse; C520853:alogliptin; C015068:1-(3-chlorophenyl)piperazine
keywords: 5-HT1B receptor agonist; Alogliptin; DPP-4; GLP-1; mCPP