MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle

In type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle resistance accounts for more than 80% of the impairment in total body glucose disposal T2D patients is often characterized by an impaired signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as key regulator cell membrane repair machinery has been suggested be critical signaling pathway acting ubiquitin E3 ligase targeting receptor substrate 1 (IRS1). Here, we show using vitro vivo approaches that MG53 not homeostasis. First, expression consistently regulated skeletal from various preclinical models resistance. Second, gene knock-down cells does lead response measured Akt phosphorylation on Serine 473 uptake. Third, recombinant human alter differentiated C2C12 cells. Fourth, ectopic HEK293 lacking endogenous fails phosphorylation. Finally, male female mg53 -/- mice were high fat induced obesity intolerance compared wild-type mice. Taken together, these results strongly suggest muscle.