Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats

Ritsuko Kawaharada, Akio Nakamura, Katsunori Takahashi, Haruhisa Kikuchi, Yoshiteru Oshima, Yuzuru Kubohara

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Aims Differentiation-inducing factor 1 (DIF-1), originally discovered in the cellular slime mold Dictyostelium discoideum, and its derivatives possess pharmacological activities, such as the promotion of glucose uptake in non-transformed mammalian cells in vitro. Accordingly, DIFs are considered promising lead candidates for novel anti-diabetic drugs. The aim of this study was to assess the anti-diabetic and toxic effects of DIF-1 in mouse 3T3-L1 fibroblast cells in vitro and in diabetic rats in vivo. Main methods We investigated the in vitro effects of DIF-1 and DIF-1(3M), a derivative of DIF-1, on glucose metabolism in 3T3-L1 cells by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We also examined the effects of DIF-1 on blood glucose levels in streptozotocin (STZ)-induced rats. Key findings. CE-TOF-MS revealed that 20 μM DIF-1 and 20 μM DIF-1(3M) promoted glucose uptake and metabolism in 3T3-L1 cells. Oral administration of DIF-1 (30 mg/kg) significantly lowered basal blood glucose levels in STZ-treated rats and promoted a decrease in blood glucose levels after oral glucose loading (2.5 g/kg) in the rats. In addition, daily oral administration of DIF-1 (30 mg/kg/day) for 1 wk significantly lowered the blood glucose levels in STZ-treated rats but did not affect their body weight and caused only minor alterations in the levels of other blood analytes. Significance These results indicate that DIF-1 may be a good lead compound for the development of anti-diabetic drugs.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalLife Sciences
Volume155
DOIs
Publication statusPublished - 2016 Jun 15

Keywords

  • Abbreviations DIF differentiation-inducing factor
  • MC methylcellulose
  • OGTT oral glucose tolerance test
  • STZ streptozotocin

ASJC Scopus subject areas

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

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