Abstract
Shc proteins play a role in energy metabolism through interaction with the insulin receptor. The aim of this study was to determine whether Shc proteins influence liver glycolysis and gluconeogenesis under both fed and fasted states. Decreased glycolytic and increased gluconeogenic and transamination enzyme activities were observed in ShcKO versus WT mice. Levels of key regulatory metabolites, such as fructose-2,6-bisphosphate, matched the activity of metabolic pathways. Protein levels of glycolytic and gluconeogenic enzymes were not different. pAMPK protein levels increased with fasting and were higher in ShcKO versus WT mice. Therefore, Shc proteins play a role in shifting the metabolism from glucose oxidation to gluconeogenesis and lipid catabolism and should be considered as regulators of fuel selection. Fuel selection and utilization could play a critical role in healthy aging. Characterization of metabolic events in ShcKO mice would help to elucidate how metabolism is influenced by these proteins.
Highlights
IntroductionP66Shc, p46Shc and p52Shc, are encoded by the Shc locus in mammals and are involved in signal transmission from growth factor receptors [1]
Three adaptor proteins, p66Shc, p46Shc and p52Shc, are encoded by the Shc locus in mammals and are involved in signal transmission from growth factor receptors [1]
The results of the present study show a decrease in capacity for glycolysis and an increase in capacity for gluconeogenesis in ShcKO versus WT mice based on the activity of key regulatory enzymes in these pathways
Summary
P66Shc, p46Shc and p52Shc, are encoded by the Shc locus in mammals and are involved in signal transmission from growth factor receptors [1]. Energy metabolism focused on the p66Shc isoform using the p66Shc KO mouse [5,6] While these mice lack p66Shc, it has been recently shown that they have decreased levels of p52Shc in all tissues and decreased levels of p46Shc in liver, skeletal muscle and heart [7]. The first evidence that Shc proteins may have an important influence on whole animal energy metabolism came from a study showing that ShcKO mice were resistant to weight gain on a high fat diet [5]. It has recently been shown that changes in enzyme activities and regulatory metabolite levels in ShcKO mice indicate a decreased capacity for glycolysis in skeletal muscle from these animals compared to wild-type controls under both fed and fasting conditions [8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
