Causal relationship between insulin resistance and sarcopenia

Abstract

Sarcopenia is a multifactorial disease characterized by reduced muscle mass and function, leading to disability, death, and other diseases. Recently, the prevalence of sarcopenia increased considerably, posing a serious threat to health worldwide. However, no clear international consensus has been reached regarding the etiology of sarcopenia. Several studies have shown that insulin resistance may be an important mechanism in the pathogenesis of induced muscle attenuation and that, conversely, sarcopenia can lead to insulin resistance. However, the causal relationship between the two is not clear. In this paper, the pathogenesis of sarcopenia is analyzed, the possible intrinsic causal relationship between sarcopenia and insulin resistance examined, and research progress expounded to provide a basis for the clinical diagnosis, treatment, and study of the mechanism of sarcopenia.

Keywords: Autophagy; Insulin resistance; Lipid infiltration; Mitochondria; Protein; Skeletal muscle.

Fig. 1

A PubMed search using the following keywords yielded a total of 3873 results. "(Insulin resistant) AND (Sarcopenia)", "Insulin amino acid skeletal muscle (() AND ()) AND ()", and "(Insulin) AND (skeletal muscle) AND (fat)". After screening, 540 repeated papers were excluded, 217 papers with the highest correlation were screened for literature reading, and experiments and treatises with high reliability were selected for citation

Fig. 2

Cell stimulation by insulin and amino acids is the main factor that affects intracellular protein synthesis and increases intracellular perfusion of amino acids. Amino acids and insulin increase the activation level of mTORC1 via different pathways. Insulin relieves the inhibitory effect of the TSC on mTORC1 primarily by increasing the activation level of AKT, while amino acids can directly activate mTORC1. An increase in the activation level of mTORC1 subsequently promotes the synthesis of myocyte proteins. Red arrows represent inhibitory effects, and blue arrows represent activating effects. PIP3 phosphatidylinositol 3,4,5-triphosphate

Fig. 3

Possible mechanisms by which lipid infiltration of myocytes leads to the development of insulin resistance