title: Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  CE-TOF-MS revealed that 20μM DIF-1 and 20μM DIF-1(3M) promoted glucose uptake and metabolism in 3T3-L1 cells. Oral administration of DIF-1 (30mg/kg) significantly lowered basal blood glucose levels in STZ-treated rats and promoted a decrease in blood glucose levels after oral glucose loading (2.5g/kg) in the rats. In addition, daily oral administration of DIF-1 (30mg/kg/day) for 1wk 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.
  
  
  CONCLUSIONS
  These results indicate that DIF-1 may be a good lead compound for the development of anti-diabetic drugs.
authors.affiliation: Department of Health and Nutrition, Faculty of Health and Welfare, Takasaki University of Health and Welfare, Takasaki 370-0033, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kawaharada
authors.affiliation: Department of Molecular Pharmacology and Oncology, Gunma University School of Medicine, Maebashi 371-8515, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Medical Technology, Faculty of Health Science, Gunma Paz College, Takasaki 370-0006, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Laboratory of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Laboratory of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
authors.affiliation: Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan; Department of Health Science, Graduate School of Health and Sports Science, Juntendo University, Inzai City 270-1695, Japan. Electronic address: ykuboha@juntendo.ac.jp.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kubohara
mesh_terms: D041721:3T3-L1 Cells; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000628:therapy; D006588:Hexanones / Q000627:therapeutic use*; D006843:Hydrocarbons, Chlorinated / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D051379:Mice; D051381:Rats; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; C490570:Differentiation-inducing factor-1, Dictyostelium; D006588:Hexanones; D006843:Hydrocarbons, Chlorinated; D007004:Hypoglycemic Agents; D013311:Streptozocin
keywords: Cellular slime mold; DIF-1; Diabetes; Dictyostelium; Streptozotocin