Cancer causes dysfunctional insulin signaling and glucose transport in a muscle‐type‐specific manner
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7932315.
This paper shows how cancer is affecting insulin-dependent glucose transport in oxidative and glycolytic muscles (in-vitro assay for glucose transport). The findings are interesting and show that cancer is causing dysfunctional insulin signaling in a fiber type-specific manner i.e., specifically dysfunctional in oxidative fibers. There are still some missing links in the study that can be fulfilled to get an even clearer picture of the process.
As the study is limited to two muscle groups only. Understanding the glucose assay as Soleus and EDL are the ones used frequently for such assay due to their shapes still western blots can be performed on other muscle groups also.
In Figure 1 they …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7932315.
This paper shows how cancer is affecting insulin-dependent glucose transport in oxidative and glycolytic muscles (in-vitro assay for glucose transport). The findings are interesting and show that cancer is causing dysfunctional insulin signaling in a fiber type-specific manner i.e., specifically dysfunctional in oxidative fibers. There are still some missing links in the study that can be fulfilled to get an even clearer picture of the process.
As the study is limited to two muscle groups only. Understanding the glucose assay as Soleus and EDL are the ones used frequently for such assay due to their shapes still western blots can be performed on other muscle groups also.
In Figure 1 they only show body weight. It would have been great if they check the weight of different muscles also (Soleus, EDL, T.A. etc.).
In Figure 1 they also report spleen weight and take it as a readout for precachexia, elevated inflammation. There is no other readout supporting that statement.
Also, there is no data for inflammation reports in muscles also. As there might be a possibility of cachexia leading to muscle weight loss therefore muscle weight data is important. And that can also show if there is a direct effect that is leading to further disruption of insulin signaling.
The changes in GLUT4 levels in soleus are significant but minimal as per their statement. While the change in glucose transport is more prominent. So, it might not be a consequence of just GLUT4.
Further, there has been no reporting of fiber typing in soleus and EDL as it might change during the course of the experiment (21 days). Fatty acid metabolism might have been explored more as only one protein was screened (FATP4).
Other findings such as AMPK activation only in EDL muscle need to be further examined.
Overall, the paper's findings are interesting and can be explored further to understand the full process deeply. It might also lead to some interventions helping muscles during Cachexia and cancer.
Competing interests
The author declares that they have no competing interests.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7033651.
This paper shows how cancer leads to different metabolic alterations in different skeletal muscles based on the oxidative or glycolytic nature of the muscle types. While induction of cancer caused insulin resistance and altered glucose uptake in the oxidative soleus muscle, the glycolytic EDS muscles were protected from such alterations via enhanced AMPK signalling. The authors have described the mechanism of insulin resistance in the cancer-induced soleus muscles as the inability of the pAKT to phosphorylate TBC1D4, which is important for GLUT4 translocation from cytosol to plasma membrane facilitating glucose uptake. The authors also mentioned a possible mechanism of the suppression of …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7033651.
This paper shows how cancer leads to different metabolic alterations in different skeletal muscles based on the oxidative or glycolytic nature of the muscle types. While induction of cancer caused insulin resistance and altered glucose uptake in the oxidative soleus muscle, the glycolytic EDS muscles were protected from such alterations via enhanced AMPK signalling. The authors have described the mechanism of insulin resistance in the cancer-induced soleus muscles as the inability of the pAKT to phosphorylate TBC1D4, which is important for GLUT4 translocation from cytosol to plasma membrane facilitating glucose uptake. The authors also mentioned a possible mechanism of the suppression of insulin resistance in EDS muscles by enhanced AMPK signalling upon cancer induction.
Comments:
1. The authors have described experiments on oxidative soleus and glycolytic EDL muscles. However, other muscle- types should also be explored, to confirm if cancer specifically causes insulin resistance in oxidative muscles only.
2. How cancer alters insulin resistance and insulin-mediated glucose uptake in only oxidative and not glycolytic muscles is not hypothesized in this report.
3. How cancer could lead to enhanced AMPK signalling in glycolytic EDS muscles also need to be clarified.
4. The glucose uptake experiment is not well described in the materials and methods section.
5. Why is the activated pAKT in the soleus muscle unable to signal for TBC1D4 phosphorylation is a question, which needs to be addressed further.
6. Whether insulin resistance in cancer-induced soleus muscles caused hyper-insulinemia can be explored further, to link type-II diabetes as one consequence of cancer. This could have been included in the discussion section.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/6545588.
This manuscript provided some new insights into cancer targets from a metabolic view that skeletal muscle could be a target. The methods and ideas are very smooth, and the data are convincing.
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