Abstract
A continuous supply of glucose is necessary to ensure proper function and survival of all organs. Plasma glucose levels are thus maintained in a narrow range around 5 mM, which is considered the physiological set point. Glucose homeostasis is controlled primarily by the liver, fat, and skeletal muscle. Following a meal, most glucose disposals occur in the skeletal muscle, whereas fasting plasma glucose levels are determined primarily by glucose output from the liver.
The balance between the utilization and production of glucose is primarily maintained at equilibrium by two opposing hormones, insulin and glucagon. In response to an elevation in plasma glucose and amino acids (after consumption of a meal), insulin is released from the beta cells of the islets of Langerhans in the pancreas. When plasma glucose falls (during fasting or exercise), glucagon is secreted by α cells, which surround the beta cells in the pancreas. Both cell types are extremely sensitive to glucose concentrations, can regulate hormone synthesis, and are released in response to small changes in plasma glucose levels. At the same time, insulin serves as the major physiological anabolic agent, promoting the synthesis and storage of glucose, lipids, and proteins and inhibiting their degradation and release back into the circulation.
This chapter will focus mainly on signal transduction mechanisms by which insulin exerts its plethora of effects in liver, muscle, and fat cells, focusing on those pathways that are crucial in the control of glucose and lipid homeostasis.
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References
Ablooglu AJ, Kohanski RA (2001) Activation of the insulin receptor’s kinase domain changes the rate-determining step of substrate phosphorylation. Biochemistry 40:504–513
Alessi DR, Pearce LR, Garcia-Martinez JM (2009) New insights into mTOR signaling: mTORC2 and beyond. Sci Signal 2:pe27. doi:10.1126/scisignal.267pe27
Araki E et al (1994) Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372:186–190. doi:10.1038/372186a0
Backer JM et al (1992) Phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J 11:3469–3479
Bandyopadhyay G et al (1997) Activation of protein kinase C (alpha, beta, and zeta) by insulin in 3T3/L1 cells. Transfection studies suggest a role for PKC-zeta in glucose transport. J Biol Chem 272:2551–2558
Baumann CA et al (2000) CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature 407:202–207. doi:10.1038/35025089
Berman HK, O’Doherty RM, Anderson P, Newgard CB (1998) Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms. J Biol Chem 273:26421–26425
Bjorgell P, Rosberg S, Isaksson O, Belfrage P (1984) The antilipolytic, insulin-like effect of growth hormone is caused by a net decrease of hormone-sensitive lipase phosphorylation. Endocrinology 115:1151–1156. doi:10.1210/endo-115-3-1151
Bradley DC, Poulin RA, Bergman RN (1993) Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo. Diabetes 42:296–306
Brady MJ, Printen JA, Mastick CC, Saltiel AR (1997) Role of protein targeting to glycogen (PTG) in the regulation of protein phosphatase-1 activity. J Biol Chem 272:20198–20204
Brady MJ, Bourbonais FJ, Saltiel AR (1998) The activation of glycogen synthase by insulin switches from kinase inhibition to phosphatase activation during adipogenesis in 3T3-L1 cells. J Biol Chem 273:14063–14066
Brady MJ, Pessin JE, Saltiel AR (1999) Spatial compartmentalization in the regulation of glucose metabolism by insulin. Trends Endocrinol Metab 10:408–413. doi:10.1016/S1043-2760(99)00201-5
Burgering BM, Coffer PJ (1995) Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376:599–602. doi:10.1038/376599a0
Carpenter CL, Cantley LC (1996) Phosphoinositide kinases. Curr Opin Cell Biol 8:153–158
Carpentier JL, Paccaud JP, Gorden P, Rutter WJ, Orci L (1992) Insulin-induced surface redistribution regulates internalization of the insulin receptor and requires its autophosphorylation. Proc Natl Acad Sci U S A 89:162–166
Chakravarty K et al (2001) Sterol regulatory element-binding protein-1c mimics the negative effect of insulin on phosphoenolpyruvate carboxykinase (GTP) gene transcription. J Biol Chem 276:34816–34823. doi:10.1074/jbc.M103310200
Cheatham B et al (1994) Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp 70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol Cell Biol 14:4902–4911
Chen XW, Leto D, Chiang SH, Wang Q, Saltiel AR (2007) Activation of RalA is required for insulin-stimulated Glut4 trafficking to the plasma membrane via the exocyst and the motor protein Myo1c. Dev Cell 13:391–404. doi:10.1016/j.devcel.2007.07.007
Chen XW et al (2011a) Exocyst function is regulated by effector phosphorylation. Nat Cell Biol 13:580–588. doi:10.1038/ncb2226
Chen XW et al (2011b) A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action. Mol Biol Cell 22:141–152. doi:10.1091/mbc.E10-08-0665
Chiang SH et al (2001) Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410:944–948
Cho H et al (2001) Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292:1728–1731
Clement S et al (2001) The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92–97. doi:10.1038/35051094
Craparo A, Freund R, Gustafson TA (1997) 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner. J Biol Chem 272:11663–11669
Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes Dev 13:2905–2927
De Fea K, Roth RA (1997) Modulation of insulin receptor substrate-1 tyrosine phosphorylation and function by mitogen-activated protein kinase. J Biol Chem 272:31400–31406
Downward J (1998) Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10:262–267
Fantin VR et al (1999) Cloning, tissue expression, and chromosomal location of the mouse insulin receptor substrate 4 gene. Endocrinology 140:1329–1337. doi:10.1210/endo.140.3.6578
Fantin VR, Wang Q, Lienhard GE, Keller SR (2000) Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis. Am J Physiol Endocrinol Metab 278:E127–E133
Fasshauer M et al (2000) Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes. J Biol Chem 275:25494–25501. doi:10.1074/jbc.M004046200
Fisher SJ, Kahn CR (2003) Insulin signaling is required for insulin’s direct and indirect action on hepatic glucose production. J Clin Invest 111:463–468. doi:10.1172/JCI16426
Foretz M, Guichard C, Ferre P, Foufelle F (1999a) Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci U S A 96:12737–12742
Foretz M et al (1999b) ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol Cell Biol 19:3760–3768
Fruman DA et al (2000) Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat Genet 26:379–382. doi:10.1038/81715
Goldstein BJ, Bittner-Kowalczyk A, White MF, Harbeck M (2000) Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. J Biol Chem 275:4283–4289
Gustafson TA, He W, Craparo A, Schaub CD, O’Neill TJ (1995) Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol 15:2500–2508
Haney PM, Levy MA, Strube MS, Mueckler M (1995) Insulin-sensitive targeting of the GLUT4 glucose transporter in L6 myoblasts is conferred by its COOH-terminal cytoplasmic tail. J Cell Biol 129:641–658
He B, Guo W (2009) The exocyst complex in polarized exocytosis. Curr Opin Cell Biol 21:537–542. doi:10.1016/j.ceb.2009.04.007
Hedo JA, Kahn CR, Hayashi M, Yamada KM, Kasuga M (1983) Biosynthesis and glycosylation of the insulin receptor. Evidence for a single polypeptide precursor of the two major subunits. J Biol Chem 258:10020–10026
Hirosumi J et al (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336. doi:10.1038/nature01137
Hu J, Liu J, Ghirlando R, Saltiel AR, Hubbard SR (2003) Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor. Mol Cell 12:1379–1389
Huang J, Imamura T, Olefsky JM (2001) Insulin can regulate GLUT4 internalization by signaling to Rab5 and the motor protein dynein. Proc Natl Acad Sci U S A 98:13084–13089. doi:10.1073/pnas.241368698
Inoki K, Li Y, Xu T, Guan KL (2003) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17:1829–1834. doi:10.1101/gad.1110003
Inoue M, Chang L, Hwang J, Chiang SH, Saltiel AR (2003) The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin. Nature 422:629–633. doi:10.1038/nature01533
Inoue M, Chiang SH, Chang L, Chen XW, Saltiel AR (2006) Compartmentalization of the exocyst complex in lipid rafts controls Glut4 vesicle tethering. Mol Biol Cell 17:2303–2311. doi:10.1091/mbc.E06-01-0030
Inukai K et al (1997) p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin. J Biol Chem 272:7873–7882
Ishikura S, Klip A (2008) Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation. Am J Physiol Cell Physiol 295:C1016–C1025. doi:10.1152/ajpcell.00277.2008
Jhun BH et al (1994) Microinjection of the SH2 domain of the 85-kilodalton subunit of phosphatidylinositol 3-kinase inhibits insulin-induced DNA synthesis and c-fos expression. Mol Cell Biol 14:7466–7475
Jiang T et al (1998) Membrane-permeant esters of phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:11017–11024
Kane S et al (2002) A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. J Biol Chem 277:22115–22118. doi:10.1074/jbc.C200198200
Kerouz NJ, Horsch D, Pons S, Kahn CR (1997) Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest 100:3164–3172. doi:10.1172/JCI119872
Kim JB et al (1998) Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 101:1–9. doi:10.1172/JCI1411
Knudsen BS, Feller SM, Hanafusa H (1994) Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk. J Biol Chem 269:32781–32787
Kohn AD, Summers SA, Birnbaum MJ, Roth RA (1996) Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem 271:31372–31378
Kotani K et al (1998) Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. Mol Cell Biol 18:6971–6982
Krook A, Moller DE, Dib K, O’Rahilly S (1996) Two naturally occurring mutant insulin receptors phosphorylate insulin receptor substrate-1 (IRS-1) but fail to mediate the biological effects of insulin. Evidence that IRS-1 phosphorylation is not sufficient for normal insulin action. J Biol Chem 271:7134–7140
Lane MD, Ronnett G, Slieker LJ, Kohanski RA, Olson TL (1985) Post-translational processing and activation of insulin and EGF proreceptors. Biochimie 67:1069–1080
Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122:3589–3594. doi:10.1242/jcs.051011
Lavan BE, Lane WS, Lienhard GE (1997) The 60-kDa phosphotyrosine protein in insulin-treated adipocytes is a new member of the insulin receptor substrate family. J Biol Chem 272:11439–11443
Lawlor MA, Alessi DR (2001) PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 114:2903–2910
Lawrence JC Jr, Roach PJ (1997) New insights into the role and mechanism of glycogen synthase activation by insulin. Diabetes 46:541–547
Lazar DF, Saltiel AR (2006) Lipid phosphatases as drug discovery targets for type 2 diabetes. Nat Rev Drug Discov 5:333–342. doi:10.1038/nrd2007
Lazar DF et al (1995) Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin. J Biol Chem 270:20801–20807
Lehr S et al (2000) Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro. Biochemistry 39:10898–10907
Lesniewski LA et al (2007) Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance. Nat Med 13:455–462. doi:10.1038/nm1550
Leto D, Saltiel AR (2012) Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol 13:383–396. doi:10.1038/nrm3351
Li J, DeFea K, Roth RA (1999) Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem 274:9351–9356
Li S, Brown MS, Goldstein JL (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci U S A 107:3441–3446. doi:10.1073/pnas.0914798107
Lin HV, Accili D (2011) Hormonal regulation of hepatic glucose production in health and disease. Cell Metab 14:9–19. doi:10.1016/j.cmet.2011.06.003
Liu J, Kimura A, Baumann CA, Saltiel AR (2002) APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. Mol Cell Biol 22:3599–3609
Lodhi IJ et al (2008) Insulin stimulates phosphatidylinositol 3-phosphate production via the activation of Rab5. Mol Biol Cell 19:2718–2728. doi:10.1091/mbc.E08-01-0105
Mauvais-Jarvis F et al (2002) Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest 109:141–149
Maxfield FR, McGraw TE (2004) Endocytic recycling. Nat Rev Mol Cell Biol 5:121–132. doi:10.1038/nrm1315
Miinea CP et al (2005) AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J 391:87–93. doi:10.1042/BJ20050887
Miki H et al (2001) Essential role of insulin receptor substrate 1 (IRS-1) and IRS-2 in adipocyte differentiation. Mol Cell Biol 21:2521–2532. doi:10.1128/MCB.21.7.2521-2532.2001
Milarski KL, Saltiel AR (1994) Expression of catalytically inactive Syp phosphatase in 3T3 cells blocks stimulation of mitogen-activated protein kinase by insulin. J Biol Chem 269:21239–21243
Mori H et al (2009) Critical role for hypothalamic mTOR activity in energy balance. Cell Metab 9:362–374. doi:10.1016/j.cmet.2009.03.005
Moskalenko S et al (2002) The exocyst is a Ral effector complex. Nat Cell Biol 4:66–72. doi:10.1038/ncb728
Moskalenko S et al (2003) Ral GTPases regulate exocyst assembly through dual subunit interactions. J Biol Chem 278:51743–51748. doi:10.1074/jbc.M308702200
Munson M, Novick P (2006) The exocyst defrocked, a framework of rods revealed. Nat Struct Mol Biol 13:577–581. doi:10.1038/nsmb1097
Muretta JM, Romenskaia I, Mastick CC (2008) Insulin releases Glut4 from static storage compartments into cycling endosomes and increases the rate constant for Glut4 exocytosis. J Biol Chem 283:311–323. doi:10.1074/jbc.M705756200
Myers MG Jr, White MF (1995) New frontiers in insulin receptor substrate signaling. Trends Endocrinol Metab 6:209–215
Myers MG Jr et al (1994a) Insulin receptor substrate-1 mediates phosphatidylinositol 3′-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. J Biol Chem 269:28783–28789
Myers MG Jr et al (1994b) Role of IRS-1-GRB-2 complexes in insulin signaling. Mol Cell Biol 14:3577–3587
Nakashima N, Sharma PM, Imamura T, Bookstein R, Olefsky JM (2000) The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J Biol Chem 275:12889–12895
Newgard CB, Brady MJ, O’Doherty RM, Saltiel AR (2000) Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1. Diabetes 49:1967–1977
Ozes ON et al (2001) A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci U S A 98:4640–4645. doi:10.1073/pnas.051042298
Pilkis SJ, Granner DK (1992) Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol 54:885–909. doi:10.1146/annurev.ph.54.030192.004321
Ribon V, Hubbell S, Herrera R, Saltiel AR (1996) The product of the cbl oncogene forms stable complexes in vivo with endogenous Crk in a tyrosine phosphorylation-dependent manner. Mol Cell Biol 16:45–52
Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel AR (1998a) A novel, multifunctional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes. Mol Cell Biol 18:872–879
Ribon V, Johnson JH, Camp HS, Saltiel AR (1998b) Thiazolidinediones and insulin resistance: peroxisome proliferatoractivated receptor gamma activation stimulates expression of the CAP gene. Proc Natl Acad Sci U S A 95:14751–14756
Rommel C et al (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013. doi:10.1038/ncb1101-1009
Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806
Sano H et al (2003) Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem 278:14599–14602
Sano H et al (2007) Rab10, a target of the AS160 Rab GAP, is required for insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane. Cell Metab 5:293–303. doi:10.1016/j.cmet.2007.03.001
Sano H, Roach WG, Peck GR, Fukuda M, Lienhard GE (2008) Rab10 in insulin-stimulated GLUT4 translocation. Biochem J 411:89–95. doi:10.1042/BJ20071318
Sano H, Peck GR, Kettenbach AN, Gerber SA, Lienhard GE (2011) Insulin-stimulated GLUT4 protein translocation in adipocytes requires the Rab10 guanine nucleotide exchange factor Dennd4C. J Biol Chem 286:16541–16545. doi:10.1074/jbc.C111.228908
Shepherd PR (2005) Mechanisms regulating phosphoinositide 3-kinase signalling in insulin-sensitive tissues. Acta Physiol Scand 183:3–12
Shimomura I et al (1999) Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci U S A 96:13656–13661
Skolnik EY et al (1993) The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J 12:1929–1936
Standaert ML et al (1997) Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes. Potential role in glucose transport. J Biol Chem 272:30075–30082
Stralfors P, Bjorgell P, Belfrage P (1984) Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin. Proc Natl Acad Sci U S A 81:3317–3321
Sugimoto S, Wandless TJ, Shoelson SE, Neel BG, Walsh CT (1994) Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1. J Biol Chem 269:13614–13622
Sun XJ et al (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352:73–77. doi:10.1038/352073a0
Sun XJ et al (1995) Role of IRS-2 in insulin and cytokine signalling. Nature 377:173–177. doi:10.1038/377173a0
Sun Y, Bilan PJ, Liu Z, Klip A (2010) Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells. Proc Natl Acad Sci U S A 107:19909–19914. doi:10.1073/pnas.1009523107
Tanti JF, Gremeaux T, Van Obberghen E, Le Marchand-Brustel Y (1994) Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3-kinase. Biochem J 304(Pt 1):17–21
Ueki K et al (2002) Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. Mol Cell Biol 22:965–977
Wick MJ, Dong LQ, Hu D, Langlais P, Liu F (2001) Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt. J Biol Chem 276:42843–42850. doi:10.1074/jbc.M102116200
Wiese RJ, Mastick CC, Lazar DF, Saltiel AR (1995) 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. J Biol Chem 270:3442–3446
Withers DJ et al (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900–904. doi:10.1038/36116
Xu Y et al (2011) Dual-mode of insulin action controls GLUT4 vesicle exocytosis. J Cell Biol 193:643–653. doi:10.1083/jcb.201008135
Yamauchi K, Milarski KL, Saltiel AR, Pessin JE (1995) Protein-tyrosine-phosphatase SHPTP2 is a required positive effector for insulin downstream signaling. Proc Natl Acad Sci U S A 92:664–668
Yamauchi T et al (1996) Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice. Mol Cell Biol 16:3074–3084
Yoon JC et al (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138. doi:10.1038/35093050
Zerial M, McBride H (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2:107–117. doi:10.1038/35052055
Zhang M, Liu J, Cheng A, Deyoung SM, Saltiel AR (2007) Identification of CAP as a costameric protein that interacts with filamin C. Mol Biol Cell 18:4731–4740. doi:10.1091/mbc.E07-06-0628
Zinker BA et al (2002) PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci U S A 99:11357–11362. doi:10.1073/pnas.142298199
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Saltiel, A.R. (2015). Insulin Signaling in the Control of Glucose and Lipid Homeostasis. In: Herzig, S. (eds) Metabolic Control. Handbook of Experimental Pharmacology, vol 233. Springer, Cham. https://doi.org/10.1007/164_2015_14
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