Effects of N-[(Trans-4-lsopropylcyclohexyl)- carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas

Hiroshi Hirose, Hiroshi Maruyama, Katsuhiko Ito, Yoshiko Seto, Koichi Kido, Kazunori Koyama, Katsuaki Dan, Takao Saruta, Ryuichi Kato

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) has a structure which differs from those of other known blood glucose-lowering agents including sulfonylureas. It has been shown that oral administration of A-4166 exerts blood glucose-lowering effects in animal in vivo studies. In the present study, we investigated the effects of A-4166 on insulin and glucagon secretion at several glucose concentrations using isolated perfused rat pancreas preparations. Both 3.0 and 30 µmol/1 A-4166 signigicantly stimulated insulin secretion as compared with basal levels at glucose concentrations of 8.0 and 11.0 mmol (p<0.01 and p<0.05, respectively). In contrast, glucagon secretion was not affected by administration of A-4166 up to 30 µmol/1 at these glucose concentrations. At a glucose concentration of 5.6 mmol/1, neither0.3 nor 3.0 µmol/1 A-4166 produced significant changes in insulin and glucagon secretion. However, A-4166 at 30 µmol/1 significantly stimulated insulin secretion and inhibited glucagon secretion as compared with basal levels (p <0.01 and p <0.01, respectively). We conclude that A-4166 at 3.0 and 30 µmol/l directly stimulates insulin secretion but has little effect on glucagon secretion in isolated perfused rat pancreas at glucose concentrations of 8.0 and 11.0 mmol/1, these results, taken together with previously published data, suggest that oral administration of A-4166 could be a useful strategy for stimulating endogenous insulin secretion in non-insulin-dependent diabetic patients.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalPharmacology
Volume48
Issue number4
DOIs
Publication statusPublished - 1994 Jan 1

Keywords

  • Blood glucose-lowering agents
  • Glucagon
  • Insulin
  • Isolated perfused rat
  • Pancreas

ASJC Scopus subject areas

  • Pharmacology

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