PREreview of Cancer causes dysfunctional insulin signaling and glucose transport in a muscle-type specific manner

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.