Simplified diagram of the insulin signaling pathway

A simplified diagram of the insulin signaling pathway. Insulin attaches to the insulin receptor which activates IRS-1. This activation leads to the recruitment of PI3K and subsequently activates Akt. ORANGE PATH: In skeletal muscle, Akt facilitates glucose uptake by moving GSVs to the plasma membrane. This process involves the activation of the GTP-bound form of RAC1. Additionally, insulin promotes glycogen synthesis by inhibiting GSK3, which activates GYS, and by inactivating glycogen phosphorylase through the dephosphorylation of phosphorylase kinase. YELLOW PATH: In adipose tissue, insulin inhibits lipolysis by decreasing the availability of gluconeogenic substrates. This suppression is thought to be mediated by PDE3B, PP1, and PP2A. PURPLE PATH: In the liver, Akt reduces gluconeogenesis by inhibiting the expression of gluconeogenic genes mediated by FOXO1. Insulin enhances hepatic glycogen synthesis by regulating GYS2 and GSK3. Moreover, insulin promotes lipogenesis by up-regulating SREBP-1c. Abbreviations: IRS-1, insulin receptor substrate-1; PI3K, phosphatidylinositol-3-OH kinase; GSVs, glucose transporter type 4 (GLUT4) storage vesicles; RAC1, Ras-related C3 botulinum toxin substrate 1; GYS, glycogen synthease; PDE3B, phosphodiesterase 3B; PP1, protein phosphatase 1; PP2A, protein phosphatase-2A; FOXO1, forkhead box O1; GSK3, glycogen synthase kinase 3; SREBP-1c, sterol regulatory element-binding protein 1c; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-trisphosphate; mTORC1, mechanistic target of rapamycin complex 1; G6PC, glucose-6-phosphatase; PEPCK, phosphoenolpyruvate carboxykinase 1; GPAT1, glycerol-3-phosphate acyltransferase 1; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase. This figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license

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Positive Effects of Physical Activity on Insulin Signaling (2024) Paulina Małkowska, et al. Curr Issues Mol Biol. 2024 Jun;46(6). Figure: F2. Homo sapiens

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