TY - JOUR
T1 - 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
AU - Nonogaki, K.
AU - Kaji, T.
N1 - Publisher Copyright:
© 2015 Elsevier Masson SAS.
PY - 2015/11
Y1 - 2015/11
N2 - Aim: 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 2.5. mg/kg and 5. mg/kg or the selective 5-HT1B receptor agonist CP94253 at 2.5. mg/kg and 5. mg/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 (2. g/kg) following the injection of saline or CP94253 (5. mg/kg) in mice treated with alogliptin. Results: Intraperitoneal injection of mCPP (2.5 and 5. mg/kg) or CP94253 (2.5 and 5. mg/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. Conclusion: 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.
AB - Aim: 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 2.5. mg/kg and 5. mg/kg or the selective 5-HT1B receptor agonist CP94253 at 2.5. mg/kg and 5. mg/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 (2. g/kg) following the injection of saline or CP94253 (5. mg/kg) in mice treated with alogliptin. Results: Intraperitoneal injection of mCPP (2.5 and 5. mg/kg) or CP94253 (2.5 and 5. mg/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. Conclusion: 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.
KW - 5-HT1B receptor agonist
KW - Alogliptin
KW - DPP-4
KW - GLP-1
KW - MCPP
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U2 - 10.1016/j.diabet.2015.06.005
DO - 10.1016/j.diabet.2015.06.005
M3 - Article
C2 - 26234524
AN - SCOPUS:84947043968
VL - 41
SP - 425
EP - 428
JO - Diabetes and Metabolism
JF - Diabetes and Metabolism
SN - 1262-3636
IS - 5
ER -