Insulin Signaling in Microdomains of the Plasma Membrane

Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction. Recent evidence suggests that compartmentalization of signaling molecules and metabolic enzymes may explain the unique cellular effects of the hormone. Signal initiation from the insulin receptor is restricted in part to caveolae microdomains of the plasma membrane. A fraction of the insulin receptor directly interacts with caveolin, thus directing the protein to caveolae. Following its activation by insulin, the receptor recruits a series of adapter proteins, resulting in the activation of the G protein TC10, which also resides in caveolae. TC10 can influence a number of cellular processes, including changes in the actin cytoskeleton, recruitment of effector including the adapter protein CIP4, and assembly of the exocyst complex. These events play crucial roles in the trafficking, docking and fusion of vesicles containing the insulin‐responsive glucose transporter Glut4 at the plasma membrane.

[1]  M. Lisanti,et al.  Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. , 2003, American journal of physiology. Cell physiology.

[2]  Alan R. Saltiel,et al.  The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin , 2003, Nature.

[3]  G. Gould,et al.  The Vesicle- and Target-SNARE Proteins That Mediate Glut4 Vesicle Fusion Are Localized in Detergent-insoluble Lipid Rafts Present on Distinct Intracellular Membranes* , 2002, The Journal of Biological Chemistry.

[4]  A. Saltiel,et al.  The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Saltiel,et al.  The Insulin Receptor Catalyzes the Tyrosine Phosphorylation of Caveolin-1* , 2002, The Journal of Biological Chemistry.

[6]  A. Saltiel,et al.  APS Facilitates c-Cbl Tyrosine Phosphorylation and GLUT4 Translocation in Response to Insulin in 3T3-L1 Adipocytes , 2002, Molecular and Cellular Biology.

[7]  A. Saltiel,et al.  Cloning and Functional Characterization of Related TC10 Isoforms, a Subfamily of Rho Proteins Involved in Insulin-stimulated Glucose Transport* , 2002, The Journal of Biological Chemistry.

[8]  P. Strålfors,et al.  Insulin induces translocation of glucose transporter GLUT4 to plasma membrane caveolae in adipocytes , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  L. Chamberlain.  Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3‐L1 adipocytes , 2001, FEBS letters.

[10]  M. Palacín,et al.  Lipid rafts are required for GLUT4 internalization in adipose cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Kanzaki,et al.  Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation , 2001, The Journal of cell biology.

[12]  A. Saltiel,et al.  The sorbin homology domain: A motif for the targeting of proteins to lipid rafts , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Makoto Kanzaki,et al.  Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10 , 2001, Nature.

[14]  M. Czech,et al.  A Role for Kinesin in Insulin-stimulated GLUT4 Glucose Transporter Translocation in 3T3-L1 Adipocytes* , 2001, The Journal of Biological Chemistry.

[15]  M. Kanzaki,et al.  CAP defines a second signalling pathway required for insulin-stimulated glucose transport , 2000, Nature.

[16]  A. Saltiel,et al.  Cloning and Characterization of a Functional Peroxisome Proliferator Activator Receptor-γ-responsive Element in the Promoter of the CAP Gene* , 2000, The Journal of Biological Chemistry.

[17]  K. Takata,et al.  Actin filaments play a critical role in insulin-induced exocytotic recruitment but not in endocytosis of GLUT4 in isolated rat adipocytes. , 2000, The Biochemical journal.

[18]  J. Engelman,et al.  Caveolins, Liquid-Ordered Domains, and Signal Transduction , 1999, Molecular and Cellular Biology.

[19]  P. Strålfors,et al.  Localization of the insulin receptor in caveolae of adipocyte plasma membrane , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  R. Henry,et al.  Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes. , 1999, The Journal of clinical investigation.

[21]  M. Kanzaki,et al.  Synip: a novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes. , 1999, Molecular cell.

[22]  J. Pessin,et al.  Molecular Basis of Insulin-stimulated GLUT4 Vesicle Trafficking , 1999, The Journal of Biological Chemistry.

[23]  J. Pessin,et al.  Regulation of Insulin-stimulated GLUT4 Translocation by Munc18c in 3T3L1 Adipocytes* , 1998, The Journal of Biological Chemistry.

[24]  M. Czech,et al.  Stimulation of IRS-1-associated Phosphatidylinositol 3-Kinase and Akt/Protein Kinase B but Not Glucose Transport by β1-Integrin Signaling in Rat Adipocytes* , 1998, The Journal of Biological Chemistry.

[25]  J. H. Johnson,et al.  Thiazolidinediones and insulin resistance: peroxisome proliferatoractivated receptor gamma activation stimulates expression of the CAP gene. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Kasuga,et al.  Requirement of Atypical Protein Kinase Cλ for Insulin Stimulation of Glucose Uptake but Not for Akt Activation in 3T3-L1 Adipocytes , 1998, Molecular and Cellular Biology.

[27]  M. Czech,et al.  Direct targets of phosphoinositide 3-kinase products in membrane traffic and signal transduction. , 1998, Trends in cell biology.

[28]  G. Joberty,et al.  Distinct cellular effects and interactions of the Rho-family GTPase TC10 , 1998, Current Biology.

[29]  Philip R. Cohen,et al.  Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. , 1998, Science.

[30]  D. James,et al.  Syndet, an Adipocyte Target SNARE Involved in the Insulin-induced Translocation of GLUT4 to the Cell Surface* , 1998, The Journal of Biological Chemistry.

[31]  M. White,et al.  The IRS-signalling system: A network of docking proteins that mediate insulin action , 1998, Molecular and Cellular Biochemistry.

[32]  R. Tsien,et al.  Membrane-permeant Esters of Phosphatidylinositol 3,4,5-Trisphosphate* , 1998, The Journal of Biological Chemistry.

[33]  G. Shulman,et al.  Disruption of IRS-2 causes type 2 diabetes in mice , 1998, Nature.

[34]  N. Hoffman,et al.  A Novel, Multifunctional c-Cbl Binding Protein in Insulin Receptor Signaling in 3T3-L1 Adipocytes , 1998, Molecular and Cellular Biology.

[35]  D. James,et al.  Moving GLUT4: The Biogenesis and Trafficking of GLUT4 Storage Vesicles , 1997, Diabetes.

[36]  G. Dohm,et al.  Mechanisms by which insulin and muscle contraction stimulate glucose transport. , 1997, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[37]  Colin B. Reese,et al.  3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase , 1997, Current Biology.

[38]  A. Saltiel,et al.  Insulin-stimulated Tyrosine Phosphorylation of Caveolin Is Specific for the Differentiated Adipocyte Phenotype in 3T3-L1 Cells* , 1997, The Journal of Biological Chemistry.

[39]  A. Saltiel,et al.  Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-Cbl in 3T3-L1 adipocytes. , 1997, The Biochemical journal.

[40]  J. Pessin,et al.  Syntaxin 4, VAMP2, and/or VAMP3/cellubrevin are functional target membrane and vesicle SNAP receptors for insulin-stimulated GLUT4 translocation in adipocytes , 1997, Molecular and cellular biology.

[41]  C. Kahn,et al.  Development of a Novel Polygenic Model of NIDDM in Mice Heterozygous for IR and IRS-1 Null Alleles , 1997, Cell.

[42]  C. Kahn,et al.  Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE-complex proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  K. Siddle,et al.  Compartment-specific regulation of phosphoinositide 3-kinase by platelet-derived growth factor and insulin in 3T3-L1 adipocytes. , 1996, The Biochemical journal.

[44]  A. Klippel,et al.  Activated Phosphatidylinositol 3-Kinase Is Sufficient to Mediate Actin Rearrangement and GLUT4 Translocation in 3T3-L1 Adipocytes* , 1996, The Journal of Biological Chemistry.

[45]  A. Klip,et al.  Adipocytes: Regulation by Insulin and Participation in Insulin-dependent Glucose Transport , 2022 .

[46]  A. Godwin,et al.  A Grb2-associated docking protein in EGF- and insulin-receptor signalling , 1996, Nature.

[47]  P. Cuatrecasas,et al.  Mitogen-activated Protein Kinase Kinase Inhibition Does Not Block the Stimulation of Glucose Utilization by Insulin (*) , 1995, The Journal of Biological Chemistry.

[48]  A. Saltiel,et al.  Insulin stimulates the tyrosine phosphorylation of caveolin , 1995, The Journal of cell biology.

[49]  A. Saltiel,et al.  Activation of Mitogen-activated Protein Kinase and Phosphatidylinositol 3′-Kinase Is Not Sufficient for the Hormonal Stimulation of Glucose Uptake, Lipogenesis, or Glycogen Synthesis in 3T3-L1 Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[50]  C. Kahn,et al.  Erratum: Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene (Nature (1994) 372 (186-190)) , 1994 .

[51]  A. Klip,et al.  Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane. , 1994, The Journal of biological chemistry.

[52]  T. Yagi,et al.  Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 , 1994, Nature.

[53]  J. Blenis,et al.  Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation , 1994, Molecular and cellular biology.

[54]  J. Olefsky,et al.  Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor. , 1994, The Journal of biological chemistry.

[55]  T. Okada,et al.  Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. , 1994, The Journal of biological chemistry.

[56]  野口 哲也.  Tyrosine phosphorylation of p62Dok induced by cell adhesion and insulin : Possible role in cell migration , 2002 .

[57]  N. Tapon,et al.  Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton. , 1997, Current opinion in cell biology.

[58]  J. Pessin,et al.  Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. , 1996, Annual review of nutrition.

[59]  C. Kahn,et al.  Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene , 1994, Nature.