Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion

Pharmacology. 1995 Oct;51(4):245-53. doi: 10.1159/000139366.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cricetinae
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / pharmacology*
  • Diazoxide / pharmacology
  • Drug Interactions
  • Glyburide / administration & dosage
  • Glyburide / pharmacology*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Mesocricetus
  • Nateglinide
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Perfusion
  • Phenylalanine / administration & dosage
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology

Substances

  • Blood Glucose
  • Cyclohexanes
  • Hypoglycemic Agents
  • Insulin
  • Vasodilator Agents
  • Nateglinide
  • Phenylalanine
  • Diazoxide
  • Glyburide