Cell Signaling & Neuroscience Insulin Pathway

Slides Programmed Cell Death Activation and Inhibition of Apoptosis Mitochondria in Apoptosis ATM/p53 Signaling Pathway Caspase Cascade Caspase Activation Intrinsic Pathway Granzyme B FAS and Related Proteins Fas Signaling G1, and S Phases G2 and M Phases Regulatory Cascade The p53 Signaling Pathway Cytokines and Growth Factors Structures of Activin and Inhibin Structures of Chemokine Receptors Angiopoietins EGFR Signaling Pathway Transmembrane Precursors of EGF Possible Receptor Combos and Ligand Actions of Flt-3/Flk-2 Hedgehog and BMI1 IGF Regulation of Apoptosis IL-13 and IL-4 receptor IL-18 Production Neurotrophins and Their Receptors TrkA GDNF Family with Receptors PDGF Receptors and Actions TGF-beta Signaling BMP Signaling TNF Signaling TNF-α and TNF-β Proposed Balance Between TNF Superfamily Structure of Receptors VEGF Receptor and Ligands Prolactin Regulation Insulin Pathway Glucocorticoid Receptor Signaling Vascular Endothelial Cell Interactions Integrin Signaling in Cell Survival VEGF Receptor Signaling MMPs and Cytokines Events Leading to Angiogenesis Transcription Factors Nuclear Complex Targeting Jak/Stat Pathway STAT3 PPAR Formation of Nucleosomes DNA Compaction Early Response Events Cell Cycle Checkpoint Linkage between DNA Repair and Chromatin Modification Functions of WRN, BLM and MRE11 mRNP Transport Importinα - Importinβ Pathway Modular Structure of Transcription factors Transcription Activation by Nuclear Receptors Coupled RNA Splicing and Nuclear Export RNA Polyadenylation Mammalian mRNA Polyadenylation RNA Maturation Epigenetic Control Phosphorylation-driven Initiation-Elongation cAMP Metabolism cGMP Metabolism G-Protein Signaling T Cell Receptor B Cell Receptor Monovalent Ion Channels Activation/Inactivation Ligand-Gated Ion Channel Aquaporin Channel Structure Calcium Channel Structure Calcium Channel Pore Region Chloride Channel HCN Channel 2TM Potassium Channel Structure 6TM Potassium Channel Structure Sodium Channel Structure Sodium Channel Pore Region PTEN Pathway Lipids in Cell Signaling Inositol Phosphates Phosphatidic Acid Inositol Phospholipids ABC Transporters ABC-ATPases BSEP MRP1 β-Amyloid Plaques Notch Secretase Second Messenger Systems Limbic Reward Circuit Major Pathways in the CNS Endothelin Signaling NPY and Catecholamines Ascending Pain Pathway Modulation of Pain Transmission Mechanism of Action Fig. A Mechanism of Action Fig. B Drug Activation of Dopaminergic GABAB Receptor Oxidative Stress nNOS eNOS iNOS Nitric Oxide Proteasome/Ubiquitination Formation of Activated 20S Proteasome Ubiquitin Pathway MAP Kinase Cascades AKT Signaling Pathways Activated by VEGF

Insulin Pathway

Signaling through the insulin pathway is critical for the regulation of intracellular and blood glucose levels and the avoidance of diabetes. Insulin binds to its receptor leading to the autophosphorylation of the b-subunits and the tyrosine phosphorylation of insulin receptor substrates (IRS). IRS phosphorylates the SH2 domain of Shp2, a tyrosine phosphatase, and the SH3 domain of the adaptor molecule Grb2. Activated Grb2 recruits Sos1 that, in turn, activates the Ras signaling pathway and gene transcription. IRS also activates phosphoinositide 3-kinase (PI3K) through its SH2 domain, thus increasing the intracellular concentration of PIP₂ and PIP. This, in turn, activates phosphatidylinositol phosphate-dependent kinase-1 (PDK-1), that subsequently activates Akt/PKB This results in the translocation of the glucose transporter (GLUT4) from cytoplasmic vesicles to the cell membrane.

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References:

Bevan, P., Insulin signalling. J. Cell Sci., 114, 1429-1430 (2001).

Kido, Y., et al., Clinical review 125: The insulin receptor and its cellular targets. J. Clin. Endocrinol. Metab., 86, 972-979 (2001).