Gene Symbol: Insr
Description: insulin receptor
Alias: 4932439J01Rik, CD220, D630014A15Rik, IR-A, IR-B, insulin receptor
Species: mouse
Products:     Insr

Top Publications

  1. Gómez Hernández A, Escribano O, Perdomo L, Otero Y, García Gómez G, Fernandez S, et al. Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-? and IGF-II. Endocrinology. 2013;154:2352-64 pubmed publisher
    To assess the role of insulin receptor (IR) isoforms (IRA and IRB) in the proliferation of vascular smooth muscle cells (VSMCs) involved in the atherosclerotic process, we generated new VSMC lines bearing IR (wild-type VSMCs; IRLoxP(+/+) ..
  2. Han S, Liang C, DeVries Seimon T, Ranalletta M, Welch C, Collins Fletcher K, et al. Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions. Cell Metab. 2006;3:257-66 pubmed
    ..signaling in macrophage foam cells might worsen atherosclerosis, Ldlr(-/-) mice were transplanted with insulin receptor Insr(+/+) or Insr(-/-) bone marrow...
  3. Nef S, Verma Kurvari S, Merenmies J, Vassalli J, Efstratiadis A, Accili D, et al. Testis determination requires insulin receptor family function in mice. Nature. 2003;426:291-5 pubmed
    ..Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igf1r and Irr, is required for the appearance of male gonads and thus ..
  4. Lin H, Kim J, Pocai A, Rossetti L, Shapiro L, Scherer P, et al. Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice. Diabetes. 2007;56:1969-76 pubmed insulin action, we analyzed adiponectin levels and activation of AMP-activated protein kinase (AMPK) in insulin receptor transgenic/knockout mice (L1), a genetic model of resistance to insulin's indirect effects on hepatic glucose ..
  5. Vicent D, Ilany J, Kondo T, Naruse K, Fisher S, Kisanuki Y, et al. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Invest. 2003;111:1373-80 pubmed
  6. Mauvais Jarvis F, Virkamaki A, Michael M, Winnay J, Zisman A, Kulkarni R, et al. A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes. Diabetes. 2000;49:2126-34 pubmed
    ..We have previously reported that isolated insulin resistance in muscle by a tissue-specific insulin receptor knockout (MIRKO mouse) is not sufficient to alter glucose homeostasis, whereas beta-cell-specific insulin ..
  7. Lauro D, Kido Y, Castle A, Zarnowski M, Hayashi H, Ebina Y, et al. Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue. Nat Genet. 1998;20:294-8 pubmed
    ..These findings indicate the need for a critical re-examination of the primary site(s) of insulin resistance in diabetes. ..
  8. Assmann A, Ueki K, Winnay J, Kadowaki T, Kulkarni R. Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2. Mol Cell Biol. 2009;29:3219-28 pubmed publisher
    ..of exogenous glucose or insulin in beta-cell lines completely lacking either insulin receptors (betaIRKO) or insulin receptor substrate 2 (betaIRS2KO)...
  9. Kulkarni R, Almind K, Goren H, Winnay J, Ueki K, Okada T, et al. Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice. Diabetes. 2003;52:1528-34 pubmed a genetically susceptible host, we generated mice that are double heterozygous (DH) for knockout of the insulin receptor and insulin receptor substrate-1 on three genetic backgrounds (C57BL/6 [B6], 129Sv, and DBA)...

More Information


  1. Koch L, Wunderlich F, Seibler J, Könner A, Hampel B, Irlenbusch S, et al. Central insulin action regulates peripheral glucose and fat metabolism in mice. J Clin Invest. 2008;118:2132-47 pubmed publisher
    ..These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. ..
  2. Duncan E, Walker S, Ezzat V, Wheatcroft S, Li J, Shah A, et al. Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species. Am J Physiol Endocrinol Metab. 2007;293:E1311-9 pubmed
    ..Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control...
  3. Fisher S, Kahn C. Insulin signaling is required for insulin's direct and indirect action on hepatic glucose production. J Clin Invest. 2003;111:463-8 pubmed
    ..we performed high-dose hyperinsulinemic-euglycemic clamps using [3-(3)H]-glucose in liver-specific insulin receptor knockout (LIRKO) mice, LIRKO mice treated with streptozotocin (LIRKO+STZ), and controls...
  4. Kido Y, Burks D, Withers D, Bruning J, Kahn C, White M, et al. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest. 2000;105:199-205 pubmed
    ..signaling pathway in these processes, we have generated mice with combined heterozygous null mutations in insulin receptor (ir), insulin receptor substrate (irs-1), and/or irs-2...
  5. Boucher J, Tseng Y, Kahn C. Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. J Biol Chem. 2010;285:17235-45 pubmed publisher
    ..before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double ..
  6. Sekimoto J, Kabayama K, Gohara K, Inokuchi J. Dissociation of the insulin receptor from caveolae during TNF?-induced insulin resistance and its recovery by D-PDMP. FEBS Lett. 2012;586:191-5 pubmed publisher
    ..Here, we analyzed the interaction between insulin receptor (IR) and GM3 in the plasma membranes using immunoelectron microscopy...
  7. Kim J, Michael M, Previs S, Peroni O, Mauvais Jarvis F, Neschen S, et al. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J Clin Invest. 2000;105:1791-7 pubmed
    ..Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are normoglycemic but have increased fat mass...
  8. Boucher J, Mori M, Lee K, Smyth G, Liew C, Macotela Y, et al. Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nat Commun. 2012;3:902 pubmed publisher
    ..Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate. ..
  9. Lin H, Plum L, Ono H, Gutierrez Juarez R, Shanabrough M, Borok E, et al. Divergent regulation of energy expenditure and hepatic glucose production by insulin receptor in agouti-related protein and POMC neurons. Diabetes. 2010;59:337-46 pubmed publisher
    ..Restoration of insulin action in AgRP neurons normalized insulin suppression of HGP. Surprisingly, POMC-specific InsR knock-in increased energy expenditure and locomotor activity, exacerbated insulin resistance and increased HGP, ..
  10. Kondo T, Vicent D, Suzuma K, Yanagisawa M, King G, Holzenberger M, et al. Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization. J Clin Invest. 2003;111:1835-42 pubmed
    ..the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO)...
  11. Escribano O, Guillen C, Nevado C, Gómez Hernández A, Kahn C, Benito M. Beta-Cell hyperplasia induced by hepatic insulin resistance: role of a liver-pancreas endocrine axis through insulin receptor A isoform. Diabetes. 2009;58:820-8 pubmed publisher
    ..address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO)...
  12. Inoue H, Ogawa W, Asakawa A, Okamoto Y, Nishizawa A, Matsumoto M, et al. Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. Cell Metab. 2006;3:267-75 pubmed
    ..These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. ..
  13. Kulkarni R, Jhala U, Winnay J, Krajewski S, Montminy M, Kahn C. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest. 2004;114:828-36 pubmed
    ..Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice--is severely ..
  14. Joshi R, Lamothe B, Cordonnier N, Mesbah K, Monthioux E, Jami J, et al. Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J. 1996;15:1542-7 pubmed
    Targeted disruption of the insulin receptor gene (Insr) in the mouse was achieved using the homologous recombination approach. Insr+/- mice were normal as shown by glucose tolerance tests...
  15. Accili D, Drago J, Lee E, Johnson M, Cool M, Salvatore P, et al. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet. 1996;12:106-9 pubmed
  16. Kulkarni R, Bruning J, Winnay J, Postic C, Magnuson M, Kahn C. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell. 1999;96:329-39 pubmed
    ..has a functional role in the beta cell we have used the Cre-loxP system to specifically inactivate the insulin receptor gene in the beta cells...
  17. Rajala R, Wiskur B, Tanito M, Callegan M, Rajala A. Diabetes reduces autophosphorylation of retinal insulin receptor and increases protein-tyrosine phosphatase-1B activity. Invest Ophthalmol Vis Sci. 2009;50:1033-40 pubmed publisher
    ..In this study, the authors examined the relationship between the retinal insulin receptor (IR) and PTP1B in normal and diabetic mouse retinas...
  18. Kabayama K, Sato T, Saito K, Loberto N, Prinetti A, Sonnino S, et al. Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance. Proc Natl Acad Sci U S A. 2007;104:13678-83 pubmed
  19. Brothers K, Wu S, DiVall S, Messmer M, Kahn C, Miller R, et al. Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor. Cell Metab. 2010;12:295-305 pubmed publisher
    ..By contrast, both lean and obese mice with a pituitary-specific knockout of the insulin receptor (PitIRKO) exhibited reproductive competency, indicating that insulin signaling in the pituitary is required ..
  20. Könner A, Janoschek R, Plum L, Jordan S, Rother E, Ma X, et al. Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab. 2007;5:438-49 pubmed
    ..insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the ..
  21. Louvi A, Accili D, Efstratiadis A. Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development. Dev Biol. 1997;189:33-48 pubmed
    ..To determine whether XR is the insulin receptor (IR), we examined embryos nullizygous for both Igf1r and Insr...
  22. DiVall S, Williams T, Carver S, Koch L, Bruning J, Kahn C, et al. Divergent roles of growth factors in the GnRH regulation of puberty in mice. J Clin Invest. 2010;120:2900-9 pubmed publisher
    ..These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. ..
  23. Pitetti J, Torre D, Conne B, Papaioannou M, Cederroth C, Xuan S, et al. Insulin receptor and IGF1R are not required for oocyte growth, differentiation, and maturation in mice. Sex Dev. 2009;3:264-72 pubmed publisher
    ..and insulin-like growth factors (IGFs: IGF1 and IGF2) act through 2 structurally related receptors, the insulin receptor (INSR) and the type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes...
  24. Tseng Y, Kokkotou E, Schulz T, Huang T, Winnay J, Taniguchi C, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008;454:1000-4 pubmed publisher
    ..These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity. ..
  25. Bluher M, Michael M, Peroni O, Ueki K, Carter N, Kahn B, et al. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell. 2002;3:25-38 pubmed
    ..Using the Cre-loxP system, we created mice with fat-specific disruption of the insulin receptor gene (FIRKO mice)...
  26. Boucher J, Macotela Y, Bezy O, Mori M, Kriauciunas K, Kahn C. A kinase-independent role for unoccupied insulin and IGF-1 receptors in the control of apoptosis. Sci Signal. 2010;3:ra87 pubmed publisher
    ..Insulin and IGF-1 binding stimulates receptor tyrosine kinase activity and blocks apoptosis, whereas unliganded IR and IGF1R, acting through a mechanism independent of their catalytic activity, exert a permissive effect on cell death. ..
  27. Rajala R, Tanito M, Neel B, Rajala A. Enhanced retinal insulin receptor-activated neuroprotective survival signal in mice lacking the protein-tyrosine phosphatase-1B gene. J Biol Chem. 2010;285:8894-904 pubmed publisher
    ..We previously demonstrated that light-induced tyrosine phosphorylation of the retinal insulin receptor (IR) results in the activation of phosphoinositide 3-kinase/Akt survival pathway in rod photoreceptor cells...
  28. Biddinger S, Hernandez Ono A, Rask Madsen C, Haas J, Aleman J, Suzuki R, et al. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab. 2008;7:125-34 pubmed publisher
    ..Liver insulin receptor knockout (LIRKO) mice have pure hepatic insulin resistance...
  29. Stachelscheid H, Ibrahim H, Koch L, Schmitz A, Tscharntke M, Wunderlich F, et al. Epidermal insulin/IGF-1 signalling control interfollicular morphogenesis and proliferative potential through Rac activation. EMBO J. 2008;27:2091-101 pubmed publisher
    ..Our results identify the small GTPase Rac as a key target of epidermal IR/IGF-1R signalling crucial for proliferative potential and interfollicular morphogenesis. ..
  30. Otani K, Kulkarni R, Baldwin A, Krutzfeldt J, Ueki K, Stoffel M, et al. Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice. Am J Physiol Endocrinol Metab. 2004;286:E41-9 pubmed
    Pancreatic beta-cell-restricted knockout of the insulin receptor results in hyperglycemia due to impaired insulin secretion, suggesting that this cell is an important target of insulin action...
  31. Okada T, Liew C, Hu J, Hinault C, Michael M, Krtzfeldt J, et al. Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance. Proc Natl Acad Sci U S A. 2007;104:8977-82 pubmed
    ..In the first model, we used liver-specific insulin receptor knockout (LIRKO) mice, which exhibit hyperinsulinemia without developing diabetes due to a compensatory ..
  32. Okamoto H, Nakae J, Kitamura T, Park B, Dragatsis I, Accili D. Transgenic rescue of insulin receptor-deficient mice. J Clin Invest. 2004;114:214-23 pubmed
    ..We show that combined restoration of insulin receptor function in brain, liver, and pancreatic beta cells rescues insulin receptor knockout mice from neonatal ..
  33. Baumgartl J, Baudler S, Scherner M, Babaev V, Makowski L, Suttles J, et al. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Cell Metab. 2006;3:247-56 pubmed the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions...
  34. Hill J, Elias C, Fukuda M, Williams K, Berglund E, Holland W, et al. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab. 2010;11:286-97 pubmed publisher
    ..We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function. ..
  35. Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest. 2002;110:1839-47 pubmed
    ..Mice lacking insulin receptor substrate-2 (Irs2) develop beta cell failure, suggesting that insulin signaling is required to maintain an ..
  36. Ferron M, Wei J, Yoshizawa T, Del Fattore A, Depinho R, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142:296-308 pubmed publisher
    The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described...
  37. Kawamori D, Kurpad A, Hu J, Liew C, Shih J, Ford E, et al. Insulin signaling in alpha cells modulates glucagon secretion in vivo. Cell Metab. 2009;9:350-61 pubmed publisher
    ..In this study, we created and characterized alpha cell-specific insulin receptor knockout (alphaIRKO) mice to directly explore the role of insulin signaling in the regulation of glucagon ..
  38. Rajala A, Tanito M, Le Y, Kahn C, Rajala R. Loss of neuroprotective survival signal in mice lacking insulin receptor gene in rod photoreceptor cells. J Biol Chem. 2008;283:19781-92 pubmed publisher
    b>Insulin receptor (IR) signaling provides a trophic signal for transformed retinal neurons in culture, but the role of IR activity in vivo is unknown...
  39. El Ouaamari A, Kawamori D, Dirice E, Liew C, Shadrach J, Hu J, et al. Liver-derived systemic factors drive ? cell hyperplasia in insulin-resistant states. Cell Rep. 2013;3:401-10 pubmed publisher
    ..and pancreatic islets modulates ? cell growth in response to insulin resistance, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia...
  40. Qiu X, Dowling A, Marino J, Faulkner L, Bryant B, Bruning J, et al. Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells. Endocrinology. 2013;154:1337-48 pubmed publisher
    ..These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states. ..
  41. Okamoto H, Obici S, Accili D, Rossetti L. Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action. J Clin Invest. 2005;115:1314-22 pubmed
    Partial restoration of insulin receptor Insr expression in brain, liver, and pancreatic beta cells is sufficient for rescuing Insr knockout mice from neonatal death, preventing diabetes ketoacidosis, and normalizing life span and ..
  42. Liu S, Okada T, Assmann A, Soto J, Liew C, Bugger H, et al. Insulin signaling regulates mitochondrial function in pancreatic beta-cells. PLoS ONE. 2009;4:e7983 pubmed publisher
    ..Mitochondria isolated from beta-cells derived from beta-cell specific insulin receptor knockout (betaIRKO) mice exhibited reduced BAD(S), GK and protein kinase A in the complex, and attenuated ..
  43. Kimura A, Mora S, Shigematsu S, Pessin J, Saltiel A. The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. J Biol Chem. 2002;277:30153-8 pubmed
    ..To explore the mechanisms involved in this event, we evaluated the association of the insulin receptor with caveolin...
  44. Ueki K, Okada T, Hu J, Liew C, Assmann A, Dahlgren G, et al. Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes. Nat Genet. 2006;38:583-8 pubmed
    ..We propose that therapeutic improvement of insulin and IGF-I signaling in beta cells might protect against type 2 diabetes. ..
  45. Leibiger B, Leibiger I, Moede T, Kemper S, Kulkarni R, Kahn C, et al. Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. Mol Cell. 2001;7:559-70 pubmed
    ..Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the betaGK gene by signaling via insulin ..
  46. Bruning J, Gautam D, Burks D, Gillette J, Schubert M, Orban P, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289:2122-5 pubmed
    ..Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction. ..
  47. Katic M, Kennedy A, Leykin I, Norris A, McGettrick A, Gesta S, et al. Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell. 2007;6:827-39 pubmed
    ..Fat-specific insulin receptor knock-out (FIRKO) mice represent an interesting dichotomy, with leanness and increased lifespan, despite ..
  48. Belke D, Betuing S, Tuttle M, Graveleau C, Young M, Pham M, et al. Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Invest. 2002;109:629-39 pubmed
    ..cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective insulin receptor knockout (CIRKO) using cre/loxP recombination...
  49. Bruning J, Winnay J, Bonner Weir S, Taylor S, Accili D, Kahn C. Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell. 1997;88:561-72 pubmed
    ..Mice double heterozygous for null alleles in the insulin receptor and insulin receptor substrate-1 genes exhibit the expected approximately 50% reduction in expression of ..
  50. Fulzele K, Riddle R, DiGirolamo D, Cao X, Wan C, Chen D, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142:309-19 pubmed publisher
    ..Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the ..
  51. Kitamura T, Kitamura Y, Nakae J, Giordano A, Cinti S, Kahn C, et al. Mosaic analysis of insulin receptor function. J Clin Invest. 2004;113:209-19 pubmed
    ..Targeted ablation of insulin receptor (Insr) has not clarified this issue, because of early postnatal lethality...
  52. Bruning J, Michael M, Winnay J, Hayashi T, Hörsch D, Accili D, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2:559-69 pubmed
    ..muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-loxP system to disrupt the insulin receptor gene in mouse skeletal muscle...
  53. Fisher S, Bruning J, Lannon S, Kahn C. Insulin signaling in the central nervous system is critical for the normal sympathoadrenal response to hypoglycemia. Diabetes. 2005;54:1447-51 pubmed
    ..system in regulating the counterregulatory response to hypoglycemia, mice with a brain/neuron-specific insulin receptor knockout (NIRKO) and littermate controls were subjected to 90-min hyperinsulinemic (20 mU x kg(-1) x min(-1)) ..
  54. Michael M, Kulkarni R, Postic C, Previs S, Shulman G, Magnuson M, et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell. 2000;6:87-97 pubmed
    ..the effect of the loss of direct insulin action in liver, we have used the Cre-loxP system to inactivate the insulin receptor gene in hepatocytes...
  55. Nakae J, Biggs W, Kitamura T, Cavenee W, Wright C, Arden K, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002;32:245-53 pubmed
    ..This has been corrected in the full-text online version of the article. The name will appear correctly in the print version. ..
  56. Tsuneki H, Murata S, Anzawa Y, Soeda Y, Tokai E, Wada T, et al. Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice. Diabetologia. 2008;51:657-67 pubmed publisher
    ..Our results demonstrate a novel role for orexin in hypothalamic insulin signalling, which is likely to be responsible for preventing the development of peripheral insulin resistance with age. ..
  57. Wheatcroft S, Shah A, Li J, Duncan E, Noronha B, Crossey P, et al. Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor. Diabetes. 2004;53:2645-52 pubmed
    ..We studied this relationship in mice heterozygous for knockout of the insulin receptor (IRKO), which have a mild perturbation of insulin signaling...
  58. Welsh G, Hale L, Eremina V, Jeansson M, Maezawa Y, Lennon R, et al. Insulin signaling to the glomerular podocyte is critical for normal kidney function. Cell Metab. 2010;12:329-340 pubmed publisher
    ..signaling in podocytes affects glomerular function in vivo, we generated mice with specific deletion of the insulin receptor from their podocytes...
  59. Harrington L, Findlay G, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004;166:213-23 pubmed
    ..maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1...
  60. Wu S, DiVall S, Wondisford F, Wolfe A. Reproductive tissues maintain insulin sensitivity in diet-induced obesity. Diabetes. 2012;61:114-23 pubmed publisher
    ..Pituitary-specific insulin receptor knockout mice were used as controls...
  61. Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A. 2004;101:3100-5 pubmed
    ..contributes to defects in neuronal function, we have performed a detailed analysis of brain/neuron-specific insulin receptor knockout (NIRKO) mice...
  62. Boudina S, Bugger H, Sena S, O Neill B, Zaha V, Ilkun O, et al. Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation. 2009;119:1272-83 pubmed publisher
    ..This study identifies specific contributions of impaired insulin action to mitochondrial dysfunction in the heart. ..
  63. Matsumoto M, Pocai A, Rossetti L, Depinho R, Accili D. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab. 2007;6:208-16 pubmed
    ..caused by generalized ablation of insulin receptors and prevents neonatal diabetes and hepatosteatosis in insulin receptor knockout mice...