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

Hiroshi Hirose, H. Maruyama, K. Ito, Y. Seto, K. Kido, K. Koyama, K. Dan, T. Saruta, R. Kato

Research output: Contribution to journalArticle

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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/l 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/l at these glucose concentrations. At a glucose concentration of 5.6 mmol/l, neither 0.3 nor 3.0 μmol/1A-4166 produced significant changes in insulin and glucagon secretion. However, A-4166 at 30 μmol/l 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
Publication statusPublished - 1994

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nateglinide
Glucagon
Pancreas
Insulin
Glucose
Oral Administration
Blood Glucose

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of N-[(trans-4-isopropylcyclohexyl)- carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas. / Hirose, Hiroshi; Maruyama, H.; Ito, K.; Seto, Y.; Kido, K.; Koyama, K.; Dan, K.; Saruta, T.; Kato, R.

In: Pharmacology, Vol. 48, No. 4, 1994, p. 205-210.

Research output: Contribution to journalArticle

Hirose, H, Maruyama, H, Ito, K, Seto, Y, Kido, K, Koyama, K, Dan, K, Saruta, T & Kato, R 1994, 'Effects of N-[(trans-4-isopropylcyclohexyl)- carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas', Pharmacology, vol. 48, no. 4, pp. 205-210.
Hirose, Hiroshi ; Maruyama, H. ; Ito, K. ; Seto, Y. ; Kido, K. ; Koyama, K. ; Dan, K. ; Saruta, T. ; Kato, R. / Effects of N-[(trans-4-isopropylcyclohexyl)- carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas. In: Pharmacology. 1994 ; Vol. 48, No. 4. pp. 205-210.
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AU - Ito, K.

AU - Seto, Y.

AU - Kido, K.

AU - Koyama, K.

AU - Dan, K.

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AU - Kato, R.

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