Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia in mice.
Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia were studied in mice. Buspirone did not affect plasma glucose levels of non-fasted mice, while it increased serum insulin levels. In fasted mice, buspirone significantly reduced glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. This suggests that buspirone enhances insulin release, resulting in inhibition of glucose-induced hyperglycemia. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) increased serum insulin levels and induced a slight hypoglycemia in non-fasted mice. 1-PP decreases glucose-induced hyperglycemia and amplifies insulin release elicited by glucose in fasted mice. Since buspirone is mainly metabolized to 1-PP and formation of 1-PP occurs quickly, the inhibitory effect of buspirone on glucose-induced hyperglycemia is likely mediated by 1-PP.
Sugimoto
Yumi
Y
Department of Pharmacology, Kobe Pharmaceutical University, Japan. yumisugi@kobepharma-u.ac.jp
Takashima
Nozomu
N
Noma
Toshiko
T
Yamada
Jun
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D002065:Buspirone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D005215:Fasting; D005947:Glucose; D006943:Hyperglycemia / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control; D006946:Hyperinsulinism / Q000517:prevention & control; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D014151:Anti-Anxiety Agents; D001786:Blood Glucose; D007328:Insulin; D017366:Serotonin Receptor Agonists; C037921:1-(2-pyrimidinyl)piperazine; D005947:Glucose; D002065:Buspirone