Pathways of Insulin Signaling

IGF IGF I IGF Gl I I I Gl Gl Gl FFA I ROS Insulin α α Hypoglycemia I Hyperinsulinemia I I Receptor Gl β β Gl IGF Gl IGF I Gl PC-1 Lipid raft TNFα PIP2 T SNARE I complex PIP3 PDK SOCS3 IRS1-4 AKT Flotillin p85 Cav CAP Syntaxin 4 PTEN PI3K Glucose BTK Shc P PI3K Torc2 SHP2 SNAP23 IGF P p110 c-Cbl Transporter Gl I CGT P Synip Crk I GRB2 APS SOS1 GRB10 P Fyn Nck P Gab1 IGF Ras P IRS-1 GTP CIP4/2 c-Raf MEK1/2 ERK BAD Jak PTP1B CrkII TRX-1 C3G TC10 Proliferation Sec6 I Differentiation PKCζ SAP97 TSC2 Rsk p70 Akt Exo70 Gl IKK S6K Sec8 IGF PIP3 PTEN Munc18c Inflamatory JNK1 Stress P PKCλ/ζ PDK 1 SHIP Metabolic RAC IGF Stress RhoGAP Rho ROCK F-actin IRE1 14-3-3 PKCλ/ζ GLUT-4 VAMP2/3 translocation Sodium ENaC SGK JNK GTP Transport Pras40 PP2A Rab Hormone sensitive PKA cAMP PDE3B PHLLP P Lipolysis lipase GLUT-4 IkB AS160 Rab4 eNos P BAD P vesicle Nitric Oxide Production Akt/PKB PFK ASIP & Vasodilation Bcl-2 Caspase 9 TSC1 TSC2 Apoptosis GSK-3 JIP1 Protor Sin1 JNK1 Rheb mTOR glycogen P Rictor GβL p38 PP1 synthase (Torc 2) SIK QSK1 ATP citrate mTOR GβL Hypoxia lyase Raptor PKC Glycogen (Torc 1) Rac QIK Synthesis ? elF2B Rho WASP BRSK1/2 LKB1 Hypoglycemia HIF-1α p70 S6K Vascular & IRE1 Fatty Acid Other effects ER Stress Synthesis 4E-BP1 IRSp53 IRS-1 PAK NUAK1/2 eNOS eIF4E Food MARK1-4 Intake Protein PDK Synthesis S6 SFK1/MKK7 MEKK1 TRAFs WAVE LIMK MLCK DNP Low Nutrient Levels eIF4B AICAR (high AMP/ATP ratio) CREB Actin P EEF2 AMPK MKK4 JNK Leptin Adiponectin XPB-1 EEF2K HMGR p300 ChREBP HSL JNK HNFα IRS-1 PFK2 Excercise Cholesterol ACC1 ERK PKA GS c-fos Synthesis c-Jun STAT1 ACC2 CFTR Lipolysis CREB Elk L-type Pyruvate Transcription STAT3 Kinase Gene Anabolism Control Expression Hypothermal Stress HIF-1α Fatty Acid Fatty Acid Ion Glycogen Synthesis Oxidation Transport Synthesis Psychosocial Nucleus STAT1 Stress UPR FAS Gene Glycolysis Insulin Receptor Expression Heart Leukocytes Sensitivity XPB-1 Apoptosis Burn Energy STAT3 Decrease Insulin FKHRL1 FOX0 AFX β-Catenin HIF-1α FFA Decrease SIRT Starvation ROS Production Response SGK Akt/PKB p53 FOX03A

PP2A UCP 1-4 PHLPP

SIRT1

MEK

FOX03A

Substrate G-protein Kinase Phosphatase Transcription Factor Activates Inhibits

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Millipore and Upstate are registered trademarks of Millipore Corporation. Fisher Lit. No. BN0419076 Printed in U.S.A. 07-182D © 2007 Millipore Corporation, Billerica, MA 01821 All rights reserved. Millipore Lit. No. PS0005EN00