Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion.
Using the in situ hamster pancreatic perfusion system, the stimulating action of A-4166 on insulin release was examined in comparison with that of glibenclamide. Both antidiabetic agents stimulated insulin release, but its onset by A-4166 was faster than that by glibenclamide. In the presence of a basal glucose concentration (3 mmol/l), insulin releases induced by A-4166 and glibenclamide were inhibited by preexisting diazoxide. At higher glucose concentrations (5-16.7 mmol/l), however, A-4166 was able to reverse the inhibitory effect of diazoxide on the first and second phases of insulin release, while glibenclamide did not reverse the first-phase release. On the other hand, in the presence of 16.7 mmol/l of glucose A-4166 completely reversed the inhibitory action of diazoxide added simultaneously, but glibenclamide reversed it only partially. In the presence of 8 mmol/l of glucose, the stimulating action of A-4166 and glibenclamide on insulin release was hardly affected by inhibitors of ATP production. These results indicate that the stimulating action of A-4166 on insulin release is different from glibenclamide in response to the inhibitory action of diazoxide. These results also suggest that A-4166 is an effective agent for release of insulin by acting on the KATP channel, especially under an impaired function of pancreatic B cells.
Seto
Y
Y
Pharmaceutical Institute, Keio University School of Medicine, Tokyo, Japan.
Fujita
H
H
Dan
K
K
Fujita
T
T
Kato
R
R
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006224:Cricetinae; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D004347:Drug Interactions; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D000077715:Nateglinide; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D014665:Vasodilator Agents; D000077715:Nateglinide; D010649:Phenylalanine; D003981:Diazoxide; D005905:Glyburide