Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study

Abstract

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Interferon regulates stem cell function at all ages by orchestrating mTOR and cell cycle

“…Indeed, we also found that the early upregulation of the activity read-out of IRS1 (Esposito et al , 2001), p-Irs1 Tyr608 , faded upon long exposure to IFN-β. Additionally, p-Irs1 Ser1134 and p-Irs1 Ser1137 displayed a biphasic trend, correlating with the activation status of mTOR (Copps & White, 2012; Karlsson et al , 2021; Langlais et al , 2011) (Appendix Table 1). This suggests that prolonged IFN-β exposure in NSCs induces negative feedback loops on Akt that ultimately inhibits mTORC1 (Fig 3B).…”

Associations between genetic loci related to lean mass and body composition in type 2 diabetes

“…16 In clear contrast to adipose tissue, the phosphorylation of IRS1 in skeletal muscle was not uniformly altered in patients with type 2 diabetes, despite the severe insulin resistance in skeletal muscle, suggesting that the posttranscriptional modification of IRS1 differs between adipose tissue and skeletal muscle in type 2 diabetes. 17 ADAMTSL3, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs)-like subfamily, is a component of the extracellular matrix and is ubiquitously expressed, including in adipose tissue and skeletal muscle. 18 Genetic association studies have consistently shown that ADAMTSL3 polymorphisms are associated with adult height 19,20 and lean mass 9,12 in humans.…”

“… 16 In clear contrast to adipose tissue, the phosphorylation of IRS1 in skeletal muscle was not uniformly altered in patients with type 2 diabetes, despite the severe insulin resistance in skeletal muscle, suggesting that the post‐transcriptional modification of IRS1 differs between adipose tissue and skeletal muscle in type 2 diabetes. 17 …”

Mass spectrometry analysis of phosphotyrosine‐containing proteins

“…The iTRAQ strategy is similar to TMT. iTRAQ and TMT quantification strategies have been used to quantify tyrosine phosphorylation signaling networks with site‐specific resolution in different biological systems, such as EGF (Marzinke et al, 2013; Tzouros et al, 2013), insulin (Karlsson et al, 2021), T‐cell receptor (Estrada et al, 2021), and other tyrosine kinases (X. Wu, Wang, et al, 2021; Zhang et al, 2010). These two quantification strategies can provide more accurate quantitative information than stable isotope label‐free methods.…”