Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes

Figure 1 Insulin signaling cascade involving both glucoregulatory and anabolic pathways. Phosphorylation sites of interest indicated on figure. Blue arrows (→) indicate activation of the substrate, orange bars (Ʇ) indicate inhibitory action on the substrate. Figure created with BioRender.com. mTOR: Mammalian target of rapamycin; mTORC: mTOR complex; S6K1: S6 kinase beta-1; IRS: Insulin receptor substrates; PKC: Protein kinase C; AMPK: AMP-activated protein kinase; TSC: Tuberous sclerosis complex; GSK-3β: Glycogen synthase kinase 3β; PIP3: phosphatidylinositol 3,4,5-triphosphates.

Figure 2 Downstream mammalian target of rapamycin complex 1 substrate S6 kinase beta-1 phosphorylation of insulin receptor substrates 1 at Ser307 and Ser636/639 leads to insulin receptor substrates 1 degradation. Blue arrows (→) indicate activation of the substrate, black arrow (→) indicates degradative pathway. Figure created with BioRender.com. S6K1: S6 kinase beta-1; IRS: Insulin receptor substrates.

Figure 3 Downstream mammalian target of rapamycin complex 1 substrate S6 kinase beta-1 is the primary kinase responsible for phosphorylation of the mammalian target of rapamycin complex 2 component Rictor at Thr1135 which has been implicated in phosphorylation of AKT at Ser473. Blue arrow (→) indicates activation of the substrate, orange bar (Ʇ) indicates inhibitory action on the substrate. Figure created with BioRender.com. mTOR: Mammalian target of rapamycin; mTORC: mTOR complex; S6K1: S6 kinase beta-1.