TY - JOUR
T1 - Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats
AU - Kawaharada, Ritsuko
AU - Nakamura, Akio
AU - Takahashi, Katsunori
AU - Kikuchi, Haruhisa
AU - Oshima, Yoshiteru
AU - Kubohara, Yuzuru
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grants (nos. 24590110 and 15K07964 to YK and YO; no. 26750054 to RK), by the Kobayashi International Scholarship Foundation (to HK), and by the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University (no. 11018 to YK, YO, and HK).
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - 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.
AB - 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.
KW - Abbreviations DIF differentiation-inducing factor
KW - MC methylcellulose
KW - OGTT oral glucose tolerance test
KW - STZ streptozotocin
UR - http://www.scopus.com/inward/record.url?scp=84970004366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84970004366&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2016.04.032
DO - 10.1016/j.lfs.2016.04.032
M3 - Article
C2 - 27131631
AN - SCOPUS:84970004366
SN - 0024-3205
VL - 155
SP - 56
EP - 62
JO - Life Sciences
JF - Life Sciences
ER -
