Insulin signaling pathway schematic

Insulin signaling pathway schematic. Insulin binds to the extracellular IR domain, inducing autophosphorylation of the intracellular domain, leading to recruitment and phosphorylation of IRS1. Regulatory subunit of PI3K, p85α, gets recruited to the bound IRS1, and activates the catalytic subunit, p110. Active PI3K converts PIP2 into PIP3 thereby recruiting PDK1 and Akt, resulting in phosphorylation of Akt on Thr308. Full activation of Akt occurs after phosphorylation on Ser473 by mTORC2. Active Akt inhibits GSK3β by Ser9 phosphorylation, therefore relieving the inhibition on Glycogen synthase (GS). Active Akt also leads to translocation of the glucose transporter GLUT4 from intracellular pools towards the membrane, where it allows glucose uptake. The stress response proteins, JNK and p38 MAPK, are activated by mitochondrial-generated ROS and result in inhibition of the insulin signaling pathway. Schematic created by Rabab Al-Lahham in BioRender.com

Publication

Tau Loss of Function, by Deletion or Aggregation, Contributes to Peripheral Insulin Resistance (2023) Rabab Al-Lahham, et al. J Alzheimers Dis. 2023 Aug 22;95(3):NA. Figure: F1. Homo sapiens

Disease mentions