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

Y. Seto, H. Fujita, K. Dan, T. Fujita, R. Kato

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 K(ATP) channel, especially under an impaired function of pancreatic B cells.

Original languageEnglish
Pages (from-to)245-253
Number of pages9
JournalPharmacology
Volume51
Issue number4
Publication statusPublished - 1995

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nateglinide
Glyburide
Cricetinae
Perfusion
Insulin
Diazoxide
Glucose
Adenosine Triphosphate
Insulin-Secreting Cells
Hypoglycemic Agents

Keywords

  • A-4166
  • Diazoxide
  • Glibenclamide
  • In situ pancreatic perfusion
  • Insulin release

ASJC Scopus subject areas

  • Pharmacology

Cite this

Seto, Y., Fujita, H., Dan, K., Fujita, T., & Kato, R. (1995). Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion. Pharmacology, 51(4), 245-253.

Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion. / Seto, Y.; Fujita, H.; Dan, K.; Fujita, T.; Kato, R.

In: Pharmacology, Vol. 51, No. 4, 1995, p. 245-253.

Research output: Contribution to journalArticle

Seto, Y, Fujita, H, Dan, K, Fujita, T & Kato, R 1995, 'Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion', Pharmacology, vol. 51, no. 4, pp. 245-253.
Seto, Y. ; Fujita, H. ; Dan, K. ; Fujita, T. ; Kato, R. / Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion. In: Pharmacology. 1995 ; Vol. 51, No. 4. pp. 245-253.
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AB - 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 K(ATP) channel, especially under an impaired function of pancreatic B cells.

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