Exploitation of the derivatives of Dictyostelium differentiation-inducing factor-1, which promote glucose consumption in mammalian cells

Yuzuru Kubohara, Haruhisa Kikuchi, Yoshiteru Oshima

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Aims: The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum. DIF-1 has also been shown to possess pharmacological activities, such as the suppression of tumor cell growth and the promotion of glucose uptake in non-transformed mammalian cells. In this study, we tried to develop compounds that possess weaker anti-tumor activity and stronger glucose uptake-promoting activity than DIF-1. Main methods: We investigated the in vitro effects of 12 derivatives of DIF-1 on glucose consumption in mouse 3T3-L1 cells and on cell growth in K562 human leukemia cells. We also examined the effect of a good compound on the blood glucose concentration in KK-Ay diabetic mice. Key findings: We found that some derivatives at 20 μM promoted glucose consumption more than twice as fast as the control. Of the derivatives, a compound named DIF-1(3M), which has a weaker anti-leukemic effect than DIF-1, promoted glucose consumption as strongly as DIF-1 in confluent 3T3-L1 cells. While DIF-1 at 20 μM was inhibitory to the cell growth of 3T3-L1, DIF-1(3M) at 20 μM exhibited no inhibitory effect on the growing cells. We also found that DIF-1(3M) injected (10-12.5 mg/kg body weight) intraperitoneally in mice tended to lower the blood glucose concentration. Significance: The present results open the possibility for the development of new agents that possess strong glucose-uptake-promoting activity but little anti-tumor activity and may have therapeutic potential for the treatment of diabetes and/or obesity.

Original languageEnglish
Pages (from-to)608-612
Number of pages5
JournalLife Sciences
Volume83
Issue number17-18
DOIs
Publication statusPublished - 2008 Oct 24

Keywords

  • Anti-tumor agent
  • Diabetes
  • Dictyostelium
  • Differentiation-inducing factor-1
  • KK-Ay mouse

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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