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The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 21, Iss 2344, p 2344 (2020), 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, vol. 21, no. 7, 2344 . https://doi.org/10.3390/ijms21072344
- Publication Year :
- 2020
-
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.
- Subjects :
- AMPK
medicine.medical_treatment
Glucose uptake
activated protein-kinase
translocation
Skeletal muscle
AMP-Activated Protein Kinases
SBI-0206965
lcsh:Chemistry
stress
Mice
Faculty of Science
Autophagy-Related Protein-1 Homolog
Insulin
lcsh:QH301-705.5
Spectroscopy
complexes
Chemistry
Kinase
Communication
General Medicine
Computer Science Applications
medicine.anatomical_structure
Benzamides
Phosphorylation
Female
ULK1/2
myopathy
energy
autophagy
medicine.medical_specialty
kinase inhibitor
ulk1
Catalysis
Inorganic Chemistry
Internal medicine
medicine
Animals
Hypoglycemic Agents
skeletal-muscle
Physical and Theoretical Chemistry
skeletal muscle
Muscle, Skeletal
Molecular Biology
Soleus muscle
Kinase inhibitor
Organic Chemistry
Glucose transporter
contraction
Biological Transport
Ribonucleotides
Aminoimidazole Carboxamide
Mice, Inbred C57BL
Endocrinology
Glucose
Pyrimidines
lcsh:Biology (General)
lcsh:QD1-999
cells
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 21
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....65f37647a67d0d9099c9a082120a5b92