Moro, T. | bioRxiv Science

bioRxiv2022

Metabolic intervention that reduces glucose-insulin signaling suppresses the onset and progression of neuroendocrine tumors

Insulin signaling often plays a role in the regulation of cancer including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We therefore investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signal within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.

cancer biology↗

bioRxiv2022

Non-invasive muscle biopsy: estimation of muscle fibre size from a neuromuscular interface

Because of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity (MUCV) could be a non-invasive index of muscle fibre size in humans. However, the relation between MUCV and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i.e., high-density surface EMG, with the gold standard technique for muscle tissue sampling, i.e., muscle biopsy, here we investigated the relation between the conduction velocity of populations of motor units identified from the biceps brachii muscle, and muscle fibre diameter. Moreover, we demonstrate the possibility to predict muscle fibre diameter (R2 = 0.66) and cross-sectional area (R2 = 0.65) from conduction velocity estimates with low systematic bias (~2% and ~4% respectively) and a relatively low margin of individual error (~8% and ~16%, respectively). The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling. The non-invasive nature of high-density surface EMG for the assessment of muscle fibre size may be useful in studies monitoring child development, aging, space and exercise physiology. SIGNIFICANCE STATEMENTOur study explored the relation between the conduction velocity of populations of motor units and muscle fibre size in healthy humans. Our results provide in vivo evidence that a high-density surface EMG-derived physiological parameter, i.e. motor unit conduction velocity, can be adopted to estimate muscle fibre size, without the need of surgical biopsy sampling. Here we propose a neuromuscular interface that opens new perspectives not only in the study of neuromuscular disorders, but also in other fields where the non-invasive and painless determination of muscle fibre and motor unit size becomes a priority, such as in aging, space and exercise physiology.

physiology↗