Antidiabetic effect of a nitrosamine-free dephostatin analogue, methoxime-3,4-dephostatin, in db/db mice

A. Hiroki, H. Hatakeyama, M. Kawakami, T. Watanabe, I. Takei, K. Umezawa

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Et-3,4-dephostatin, a protein-tyrosine phosphatase (PTPase) inhibitor, potentiates insulin-dependent signal transduction and shows an antidiabetic effect in mice. However, it contains a nitrosamine moiety that is often mutagenic and carcinogenic. Therefore, we previously designed and synthesized methoxime-3,4-dephostatin as a nitrosamine-free analogue of dephostatin. In the present paper, we studied in situ and in vivo antidiabetic effects of this PTPase inhibitor. Methoxime-3,4-dephostatin induced 2-deoxyglucose transport by mouse 3T3-L1 adipocytes and rat L6 myocytes without insulin. It also inhibited glucagon-induced glucose release from primary culture rat hepatocytes. When hepatocytes were prepared from starved rats, methoxime-3,4-dephostatin did not inhibit the release of glucose, indicating that the chemical may act on glycogenolysis. Oral administration of methoxime-3,4-dephostatin for 3-7 days inhibited the increase in the blood glucose level in type-2 diabetes model db/db mice. It also decreased food and water intakes of mice, but showed no liver or blood toxicity.

Original languageEnglish
Pages (from-to)179-185
Number of pages7
JournalBiomedicine and Pharmacotherapy
Issue number4
Publication statusPublished - 2002
Externally publishedYes


  • 3T3-L1 adipocyte
  • Dephostatin
  • Hepatocyte
  • Insulin
  • L6 myocyte
  • PTP-1B
  • db/db Mouse

ASJC Scopus subject areas

  • Pharmacology


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