Dictyostelium differentiation-inducing factor-1 induces glucose transporter 1 translocation and promotes glucose uptake in mammalian cells.
The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum, while DIF-1 and its analogs have been shown to possess antiproliferative activity in vitro in mammalian tumor cells. In the present study, we investigated the effects of DIF-1 and its analogs on normal (nontransformed) mammalian cells. Without affecting the cell morphology and cell number, DIF-1 at micromolar levels dose-dependently promoted the glucose uptake in confluent 3T3-L1 fibroblasts, which was not inhibited with wortmannin or LY294002 (inhibitors for phosphatidylinositol 3-kinase). DIF-1 affected neither the expression level of glucose transporter 1 nor the activities of four key enzymes involved in glucose metabolism, such as hexokinase, fluctose 6-phosphate kinase, pyruvate kinase, and glucose 6-phosphate dehydrogenase. Most importantly, stimulation with DIF-1 was found to induce the translocation of glucose transporter 1 from intracellular vesicles to the plasma membranes in the cells. In differentiated 3T3-L1 adipocytes, DIF-1 induced the translocation of glucose trasporter 1 (but not of glucose transporter 4) and promoted glucose uptake, which was not inhibited with wortmannin. These results indicate that DIF-1 induces glucose transporter 1 translocation and thereby promotes glucose uptake, at least in part, via a inhibitors for phosphatidylinositol 3-kinase/Akt-independent pathway in mammalian cells. Furthermore, analogs of DIF-1 that possess stronger antitumor activity than DIF-1 were less effective in promoting glucose consumption, suggesting that the mechanism of the action of DIF-1 for stimulating glucose uptake should be different from that for suppressing tumor cell growth.
Omata
Waka
W
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Shibata
Hiroshi
H
Nagasawa
Masahiro
M
Kojima
Itaru
I
Kikuchi
Haruhisa
H
Oshima
Yoshiteru
Y
Hosaka
Kohei
K
Kubohara
Yuzuru
Y
D041721:3T3-L1 Cells; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D006588:Hexanones / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D021381:Protein Transport
C490570:Differentiation-inducing factor-1, Dictyostelium; D004791:Enzyme Inhibitors; D051246:Glucose Transport Proteins, Facilitative; D006588:Hexanones; D006843:Hydrocarbons, Chlorinated; D005947:Glucose; D002118:Calcium