The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport

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Standard

The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport. / Knudsen, Jonas Roland; Madsen, Agnete B; Persson, Kaspar W; Henríquez-Olguín, Carlos; Li, Zhencheng; Jensen, Thomas Elbenhardt.

I: International Journal of Molecular Sciences, Bind 21, Nr. 7, 2344, 2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Knudsen, JR, Madsen, AB, Persson, KW, Henríquez-Olguín, C, Li, Z & Jensen, TE 2020, 'The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport', International Journal of Molecular Sciences, bind 21, nr. 7, 2344. https://doi.org/10.3390/ijms21072344

APA

Knudsen, J. R., Madsen, A. B., Persson, K. W., Henríquez-Olguín, C., Li, Z., & Jensen, T. E. (2020). The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport. International Journal of Molecular Sciences, 21(7), [2344]. https://doi.org/10.3390/ijms21072344

Vancouver

Knudsen JR, Madsen AB, Persson KW, Henríquez-Olguín C, Li Z, Jensen TE. The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport. International Journal of Molecular Sciences. 2020;21(7). 2344. https://doi.org/10.3390/ijms21072344

Author

Knudsen, Jonas Roland ; Madsen, Agnete B ; Persson, Kaspar W ; Henríquez-Olguín, Carlos ; Li, Zhencheng ; Jensen, Thomas Elbenhardt. / The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport. I: International Journal of Molecular Sciences. 2020 ; Bind 21, Nr. 7.

Bibtex

@article{875773105b7c4784a6be671124a746c3,
title = "The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport",
abstract = "The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on analog 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated AMPK-dependent glucose transport and insulin-stimulated AMPK-independent glucose uptake. Pre-treatment with 10 µM SBI-0206965 for 50 min potently suppressed AICAR-stimulated glucose transport in both the extensor digitorum longus (EDL) and soleus muscle. This was despite only a modest lowering of AICAR-stimulated AMPK activation measured as ACC2 Ser212, while ULK1/2 Ser555 phosphorylation was prevented. Insulin-stimulated glucose transport was also potently inhibited by SBI-0206965 in soleus. No major changes were observed on insulin-stimulated cell signaling. No general effect of SBI-0206965 on intracellular membrane morphology was observed by transmission electron microscopy. As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.",
keywords = "Faculty of Science, AMPK, ULK1/2, Skeletal muscle, Kinase inhibitor, SBI-0206965",
author = "Knudsen, {Jonas Roland} and Madsen, {Agnete B} and Persson, {Kaspar W} and Carlos Henr{\'i}quez-Olgu{\'i}n and Zhencheng Li and Jensen, {Thomas Elbenhardt}",
note = "CURIS 2020 NEXS 138",
year = "2020",
doi = "10.3390/ijms21072344",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences (CD-ROM)",
issn = "1424-6783",
publisher = "M D P I AG",
number = "7",

}

RIS

TY - JOUR

T1 - The ULK1/2 and AMPK inhibitor SBI-0206965 blocks AICAR and insulin-stimulated glucose transport

AU - Knudsen, Jonas Roland

AU - Madsen, Agnete B

AU - Persson, Kaspar W

AU - Henríquez-Olguín, Carlos

AU - Li, Zhencheng

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2020 NEXS 138

PY - 2020

Y1 - 2020

N2 - The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on analog 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated AMPK-dependent glucose transport and insulin-stimulated AMPK-independent glucose uptake. Pre-treatment with 10 µM SBI-0206965 for 50 min potently suppressed AICAR-stimulated glucose transport in both the extensor digitorum longus (EDL) and soleus muscle. This was despite only a modest lowering of AICAR-stimulated AMPK activation measured as ACC2 Ser212, while ULK1/2 Ser555 phosphorylation was prevented. Insulin-stimulated glucose transport was also potently inhibited by SBI-0206965 in soleus. No major changes were observed on insulin-stimulated cell signaling. No general effect of SBI-0206965 on intracellular membrane morphology was observed by transmission electron microscopy. As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.

AB - The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on analog 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated AMPK-dependent glucose transport and insulin-stimulated AMPK-independent glucose uptake. Pre-treatment with 10 µM SBI-0206965 for 50 min potently suppressed AICAR-stimulated glucose transport in both the extensor digitorum longus (EDL) and soleus muscle. This was despite only a modest lowering of AICAR-stimulated AMPK activation measured as ACC2 Ser212, while ULK1/2 Ser555 phosphorylation was prevented. Insulin-stimulated glucose transport was also potently inhibited by SBI-0206965 in soleus. No major changes were observed on insulin-stimulated cell signaling. No general effect of SBI-0206965 on intracellular membrane morphology was observed by transmission electron microscopy. As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.

KW - Faculty of Science

KW - AMPK

KW - ULK1/2

KW - Skeletal muscle

KW - Kinase inhibitor

KW - SBI-0206965

U2 - 10.3390/ijms21072344

DO - 10.3390/ijms21072344

M3 - Journal article

C2 - 32231045

VL - 21

JO - International Journal of Molecular Sciences (CD-ROM)

JF - International Journal of Molecular Sciences (CD-ROM)

SN - 1424-6783

IS - 7

M1 - 2344

ER -

ID: 241041113