The Study
CaMKK2 is not involved in contraction-stimulated AMPK activation and glucose uptake in skeletal muscle
This study is like testing if a specific key opens a lock by trying it and seeing it doesn’t work — but only in one lock in one house. It doesn’t prove the key won’t work in other locks or other houses. So we can say this key doesn’t open this one lock, but we can’t say it’s useless everywhere.
Analysis score
Maximum 72 for a cohort study.
Where the score came from
When muscles contract during exercise, they need to take in sugar for energy. Scientists thought a protein called CaMKK2 helped with this, but this study shows it's not needed.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 514 / 100
Quality score
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
Key takeaways
Summary
Based on the study abstract and findings.
- 1Yes—this means previous studies using these drugs were wrong about CaMKK2's role; the real mechanism is still unknown but doesn't involve CaMKK2.
- 2Muscles from mice without CaMKK2 took up sugar just as well as normal muscles during contraction.
- 3Two different drugs meant to block CaMKK2 also blocked sugar uptake—but so did a fake version of the drug that couldn't block CaMKK2 at all.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
Molecular Metabolism
Year
2023
Authors
Florentina Negoita, A. Addinsall, Kristina Hellberg, Conchita Fraguas Bringas, Paul S. Hafen, Tyler J Sermersheim, Marianne Agerholm, Christopher T. A. Lewis, Danial Ahwazi, Naomi X. Y. Ling, J. K. Larsen, A. Deshmukh, M. A. Hossain, J. Oakhill, J. Ochala, J. Brault, Uma Sankar, D. Drewry, J. Scott, C. Witczak, K. Sakamoto
Related Content
Claims (6)
When muscles contract, they trigger cellular mechanisms that move GLUT4 transporters to the cell surface, allowing glucose to enter muscle cells even when insulin is not present.
C2C12 muscle cells in culture produce CaMKK2 protein, but adult mouse skeletal muscle does not produce detectable levels of this protein and instead produces AMPKα2. This difference means results from C2C12 cells may not apply to real muscle tissue in adult mice.
In adult mice, blocking or removing the CaMKK2 protein does not reduce the activation of AMPK or the uptake of glucose in skeletal muscle during muscle contraction.
STO-609, a compound used to block CaMKK2, reduces glucose uptake in mouse skeletal muscle during contraction because it directly blocks AMPK and other kinases, and a chemically similar but inactive version of STO-609 produces the same effect.
In adult mouse skeletal muscle, the CaMKK2 protein cannot be detected by highly sensitive laboratory methods, even though small amounts of its genetic blueprint (mRNA) are present.
SGC-CAMKK2-1 reduces glucose uptake in mouse skeletal muscle regardless of whether the uptake is triggered by insulin or AMPK activators, and an inactive version of the compound has the same effect.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.