dictyNews
Electronic Edition
Volume 47, number 6
February 26, 2021
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Abstracts
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Dictyostelium Differentiation-Inducing Factor-1 Promotes Glucose
Uptake, at Least in Part, via an AMPK-Dependent Pathway in
Mouse 3T3-L1 Cells
Yuzuru Kubohara 1,*, Yoshimi Homma 2, Hiroshi Shibata 3, Yoshiteru
Oshima 4, Haruhisa Kikuchi 4
1 Laboratory of Health and Life Science, Graduate School of Health
and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
2 Department of Biomolecular Science, Institute of Biomedical Sciences,
Fukushima Medical University School of Medicine, Fukushima 960-1295,
Japan
3 Laboratory of Epigenetics and Metabolism, Institute for Molecular and
Cellular Regulation, Gunma University, Gunma 371-8512, Japan
4 Laboratory of Natural Product Chemistry, Graduate School of
Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki,
Aoba-ku, Sendai 980-8578, Japan
Int. J. Mol. Sci. 22, 2293. (2021).
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 glu-cose 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
microM 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 microM 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 com-pound 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.
submitted by: Yuzuru Kubohara [[log in to unmask]]
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