Dictyostelium differentiation-inducing factor-1 promotes glucose uptake, at least in part, via an ampk-dependent pathway in mouse 3t3-l1 cells

Yuzuru Kubohara, Yoshimi Homma, Hiroshi Shibata, Yoshiteru Oshima, Haruhisa Kikuchi

Research output: Contribution to journalArticlepeer-review

Abstract

Differentiation-inducing factor-1 (DIF-1) is a chlorinated alkylphenone (a polyketide) found in the cellular slime mold Dictyostelium discoideum. DIF-1 and its derivative, DIF-1(3M) promote glucose consumption in vitro in mammalian cells and in vivo in diabetic rats; they are expected to be the leading antiobesity and antidiabetes compounds. In this study, we investigated the mechanisms underlying the actions of DIF-1 and DIF-1(3M). In isolated mouse liver mitochondria, these compounds at 2–20 μM promoted oxygen consumption in a dose-dependent manner, suggesting that they act as mitochondrial uncouplers, whereas CP-DIF-1 (another derivative of DIF-1) at 10–20 μM had no effect. In confluent mouse 3T3-L1 fibroblasts, DIF-1 and DIF-1(3M) but not CP-DIF-1 induced phosphorylation (and therefore activation) of AMP kinase (AMPK) and promoted glucose consumption and metabolism. The DIF-induced glucose consumption was reduced by compound C (an AMPK inhibitor) or AMPK knock down. These data suggest that DIF-1 and DIF-1(3M) promote glucose uptake, at least in part, via an AMPK-dependent pathway in 3T3-L1 cells, whereas cellular metabolome analysis revealed that DIF-1 and DIF-1(3M) may act differently at least in part.

Original languageEnglish
Article number2293
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume22
Issue number5
DOIs
Publication statusPublished - 2021 Mar 1
Externally publishedYes

Keywords

  • AMP kinase
  • DIF-1
  • Diabetes
  • Dictyostelium discoideum
  • Obesity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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