INS and Insulin resistance: Laurent et al. (2013b) have reported that SIRT4 KO mice showed increased exercise tolerance, suggesting that SIRT4 may be involved in metabolic reprogramming during exercise training. Because high mitochondrial flux and increased fatty acid oxidation are associated with the phenotypes of insulin resistance model (Koves et al., 2008; Sunny et al., 2011); therefore, it will be of great significance to clarify the role of SIRT4 in regulating glucose and insulin homeostasis and to further investigate the potential therapeutic effects of modulating SIRT4 function by exercise.