The twentieth century struggle to decipher insulin signalling

Following the discovery of insulin, it took the rest of the twentieth century to understand how this hormone regulates intracellular metabolism. What are the main discoveries that led to our current understanding of this process? And how is this new knowledge being exploited in an attempt to develop improved drugs to treat the epidemic of type-2 diabetes?

[1]  M. J. Newman,et al.  Structure-based Design of Selective and Potent Inhibitors of Protein-tyrosine Phosphatase β* , 2004, Journal of Biological Chemistry.

[2]  P. Cohen,et al.  Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. , 1980, European journal of biochemistry.

[3]  R. Hresko,et al.  mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes* , 2005, Journal of Biological Chemistry.

[4]  T. Okada,et al.  Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase. , 1994, The Journal of biological chemistry.

[5]  A. Saltiel,et al.  Lipid phosphatases as drug discovery targets for type 2 diabetes , 2006, Nature Reviews Drug Discovery.

[6]  J. Larner,et al.  Insulin-mediated effect on the activity of UDPG-glycogen transglucosylase of muscle. , 1960, Biochimica et biophysica acta.

[7]  L. Cantley,et al.  Activation of phosphatidylinositol 3-kinase by insulin. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Maria Deak,et al.  Crystal Structure of the PTPL1/FAP-1 Human Tyrosine Phosphatase Mutated in Colorectal Cancer , 2004, Journal of Biological Chemistry.

[9]  C. Kahn,et al.  From mice to men: insights into the insulin resistance syndromes. , 2006, Annual review of physiology.

[10]  W Ogawa,et al.  Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt , 1999, Molecular and Cellular Biology.

[11]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[12]  Y. Ebina,et al.  Insulin-stimulated GLUT4 translocation is relevant to the phosphorylation of IRS-1 and the activity of PI3-kinase. , 1993, Biochemical and biophysical research communications.

[13]  S. Dowler,et al.  Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity. , 2001, The Biochemical journal.

[14]  M. Cobb,et al.  Insulin activates a tyrosine-specific protein kinase in extracts of 3T3-L1 adipocytes and human placenta. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Cushman,et al.  Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. , 1980, The Journal of biological chemistry.

[16]  P. Cohen,et al.  Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. , 1993, The Biochemical journal.

[17]  Michel Goedert,et al.  GSK3 inhibitors: development and therapeutic potential , 2004, Nature Reviews Drug Discovery.

[18]  P. Cohen,et al.  Glycogen synthase kinase-3 from rabbit skeletal muscle. , 2005, Methods in enzymology.

[19]  C. Kahn,et al.  Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells , 1985, Nature.

[20]  D. James,et al.  Molecular cloning and characterization of an insulin-regulatable glucose transporter , 1989, Nature.

[21]  C G Armstrong,et al.  Identification of the separate domains in the hepatic glycogen-targeting subunit of protein phosphatase 1 that interact with phosphorylase a, glycogen and protein phosphatase 1. , 1998, The Biochemical journal.

[22]  R. Aebersold,et al.  Isolation and characterization of the 160,000-Da phosphotyrosyl protein, a putative participant in insulin signaling. , 1991, The Journal of biological chemistry.

[23]  S. Dowler,et al.  Crystal structure of the phosphatidylinositol 3 , 4-bisphosphate-binding pleckstrin homology ( PH ) domain of tandem PH-domain-containing protein 1 ( TAPP 1 ) : molecular basis of lipid specificity , 2022 .

[24]  D. Hardie,et al.  AMPK: a key sensor of fuel and energy status in skeletal muscle. , 2006, Physiology.

[25]  C. Kahn,et al.  Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. , 1982, Science.

[26]  B. Margolis,et al.  Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. , 1992, The EMBO journal.

[27]  P. Cohen,et al.  Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα , 1997, Current Biology.

[28]  D. V. van Aalten,et al.  PDK1, the master regulator of AGC kinase signal transduction. , 2004, Seminars in cell & developmental biology.

[29]  S. Volinia,et al.  Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit , 1992, Cell.

[30]  Kei Sakamoto,et al.  Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction , 2005, The EMBO journal.

[31]  P. Taylor,et al.  An inositol tetrakisphosphate-containing phospholipid in activated neutrophils , 1988, Nature.

[32]  D. Guertin,et al.  Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex , 2005, Science.

[33]  F. McCormick,et al.  Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. , 1997, Science.

[34]  I. Singer,et al.  Effect of insulin on the phosphorylation of adipose tissue protein. , 1974, Biochimica et biophysica acta.

[35]  D. Alessi,et al.  Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. , 1996, The Biochemical journal.

[36]  Jianping Ye,et al.  Serine Phosphorylation of Insulin Receptor Substrate 1 by Inhibitor κB Kinase Complex* 210 , 2002, The Journal of Biological Chemistry.

[37]  M. Owen,et al.  Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. , 2000, The Biochemical journal.

[38]  M. Goldstein,et al.  The action of insulin on the distribution of galactose in eviscerated nephrectomized dogs. , 1949, The Journal of biological chemistry.

[39]  Margaret S. Wu,et al.  Role of AMP-activated protein kinase in mechanism of metformin action. , 2001, The Journal of clinical investigation.

[40]  J. Larner,et al.  Influence Of Epinephrine and Insulin on Uridine Diphosphate Glucose-α-Glucan Transferase and Phosphorylase in Muscle , 1964, Nature.

[41]  V. Lefebvre,et al.  Signaling Pathway Involved in the Activation of Heart 6-Phosphofructo-2-kinase by Insulin* , 1996, The Journal of Biological Chemistry.

[42]  Andrius Kazlauskas,et al.  The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase , 1995, Cell.

[43]  P. Cohen,et al.  Mechanism of activation of protein kinase B by insulin and IGF‐1. , 1996, The EMBO journal.

[44]  D. Alessi,et al.  Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis , 2005, The EMBO journal.

[45]  C. Kahn,et al.  Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase. , 1991, The Journal of biological chemistry.

[46]  M. Birnbaum Identification of a novel gene encoding an insulin-responsive glucose transporter protein , 1989, Cell.

[47]  B. Kennedy,et al.  Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. , 1999, Science.

[48]  B. Burgering,et al.  Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction , 1995, Nature.

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

[50]  C. Proud,et al.  Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B. , 1993, The Biochemical journal.

[51]  K. Kaestner,et al.  Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ) , 2001 .

[52]  H G Hers,et al.  The control of glycogen metabolism in the liver. , 1976, Annual review of biochemistry.

[53]  P. Cohen,et al.  Purification of the hepatic glycogen‐associated form of protein phosphatase‐1 by microcystin‐Sepharose affinity chromatography , 1995, FEBS letters.

[54]  M. White,et al.  Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity , 1987, Cell.

[55]  A. Prescott,et al.  Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1. , 2003, The Biochemical journal.

[56]  E. Hafen,et al.  6 Growth Regulation by Insulin and TOR Signaling in Drosophila , 2004 .

[57]  Alexandros Tzatsos,et al.  Nutrients Suppress Phosphatidylinositol 3-Kinase/Akt Signaling via Raptor-Dependent mTOR-Mediated Insulin Receptor Substrate 1 Phosphorylation , 2006, Molecular and Cellular Biology.

[58]  V. Fried,et al.  cDNA cloning of a Novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF β-receptor , 1991, Cell.

[59]  J. Woodgett,et al.  Identification of multifunctional ATP-citrate lyase kinase as the alpha-isoform of glycogen synthase kinase-3. , 1992, The Biochemical journal.

[60]  P. Cohen,et al.  Glycogen synthase from rabbit skeletal muscle; effect of insulin on the state of phosphorylation of the seven phosphoserine residues in vivo. , 2005, European journal of biochemistry.

[61]  P. Cohen,et al.  Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase‐1 , 1986, FEBS letters.

[62]  P. Cohen,et al.  Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase‐1 and p70 S6 kinase , 1996, FEBS letters.

[63]  M. Raff,et al.  Cell growth : control of cell size , 2004 .

[64]  B. Jeanrenaud,et al.  Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane. , 1981, The Journal of biological chemistry.

[65]  M. Bollen,et al.  Loss of the hepatic glycogen-binding subunit (GL) of protein phosphatase 1 underlies deficient glycogen synthesis in insulin-dependent diabetic rats and in adrenalectomized starved rats. , 1998, The Biochemical journal.

[66]  P. Cohen,et al.  The α‐isoform of glycogen synthase kinase‐3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase‐activated protein kinase‐1 in vitro , 1994, FEBS letters.

[67]  A. Arcaro,et al.  Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. , 1993, The Biochemical journal.

[68]  D. James,et al.  Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein , 1988, Nature.

[69]  P. Cohen,et al.  Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B , 1995, Nature.

[70]  G. Panayotou,et al.  Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase , 1991, Cell.

[71]  A. Prescott,et al.  Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates , 2004, The EMBO journal.

[72]  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.

[73]  R. DePinho,et al.  The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin , 2005, Science.

[74]  L. Cantley,et al.  Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate , 1988, Nature.

[75]  P. Cohen,et al.  Glycogen synthetase kinase 2 (GSK 2); The identification of a new protein kinase in skeletal muscle , 1974, FEBS letters.

[76]  P. Cohen,et al.  Glycogen Synthase from Rabbit Skeletal Muscle , 2005 .

[77]  Michael Karin,et al.  A central role for JNK in obesity and insulin resistance , 2002, Nature.

[78]  A. Ullrich,et al.  Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases , 1991, Cell.

[79]  J. Blenis,et al.  Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. , 2002, Molecular cell.

[80]  C. Kahn,et al.  Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein , 1991, Nature.

[81]  M. Kasuga,et al.  Inhibition of the translocation of GLUT1 and GLUT4 in 3T3-L1 cells by the phosphatidylinositol 3-kinase inhibitor, wortmannin. , 1994, The Biochemical journal.

[82]  M. White,et al.  Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1 , 1993, Molecular and cellular biology.

[83]  T. Kôno,et al.  Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[84]  G. Shulman,et al.  Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. , 1999, Diabetes.

[85]  J. Larner,et al.  STUDIES ON UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE. III. INTERCONVERSION OF TWO FORMS OF MUSCLE UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE BY A PHOSPHORYLATION-DEPHOSPHORYLATION REACTION SEQUENCE. , 1963, Biochemistry.

[86]  P. Taylor,et al.  Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils. , 1989, The Journal of biological chemistry.

[87]  S. Kane,et al.  Full intracellular retention of GLUT4 requires AS160 Rab GTPase activating protein. , 2005, Cell metabolism.