title: Effects of S 21403 on hormone secretion from isolated rat pancreas at different glucose concentrations.
abstract: We investigated the in vitro effects of therapeutical concentrations of S 21403 (a succinic acid derivative also known as KAD 1229 and mitiglinide) on insulin and glucagon secretion during a metabolic stimulus (glucose rising from 5 to 8.33 mM) or at a stable 2.22 mM glucose using the isolated perfused rat pancreas model, and we compared them with the patterns of repaglinide and glibenclamide. Control perfusions were also performed. During 8.33 mM glucose, insulin release peaked to 339.12+/-22.87 microU/ml in controls. S 21403 enhanced insulin release (first peak 413.02+/-14.90 microU/ml; P<0.03 vs. controls, P=ns vs. repaglinide, P<0.005 vs. glibenclamide). Repaglinide increased glucose-induced first peak secretion to 409.33+/-20.05 microU/ml within the eighth minute (P<0.05 vs. controls, P<0.01 vs. glibenclamide). Glibenclamide did not affect the first phase of glucose-induced insulin release (peak of 338.41+/-29.79 microU/ml) but potentiated and delayed the second phase. No drug affected glucagon release. In conclusion, S 21403 induces a faster, more physiological pattern of insulin release than the other drugs we tested.
authors.affiliation: Anti-Diabetic Unit, Medical Department E. Profili General Hospital, 60044 Fabriano, AN, Italy. franco.gregorio@tin.it
authors.forename: Franco
authors.initials: F
authors.lastname: Gregorio
authors.forename: Franca
authors.initials: F
authors.lastname: Ambrosi
authors.forename: Massimo
authors.initials: M
authors.lastname: Boemi
authors.forename: Flavia
authors.initials: F
authors.lastname: Carle
authors.forename: Paolo
authors.initials: P
authors.lastname: Filipponi
mesh_terms: D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D054833:Isoindoles; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D054833:Isoindoles; D010880:Piperidines; C072379:repaglinide; C087255:mitiglinide; D005947:Glucose; D005905:Glyburide