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Zentrum für Nephrologie und Stoffwechsel
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Insulinresistenz

Unter Insulinresistenz wird das Fehlende oder ungenügende Ansprechen verschiedener Stoffwechselprozesse auf das Hormon Insulin verstanden. Da das Insulin in sehr unterschiedlichen Stoffwechselwegen regulierend eingreifen kann sind die klinischen Erscheinungen vielgestaltig. Oft wird jedoch eine Insulinresistenz im Zusammenhang mit einem Diabetes mellitus und einer Lipodystrophie gesehen.

Gliederung

Diabetes mellitus
Diabetische Nephropathie
Diabetische Retinopathie
Erbliche Diabetesneigung
Gestationsdiabetes
Insulinresistenz
CIDEC
Diabetes mellitus mit Insulinresistenz und Acanthosis nigricans
INSR
ENPP1
IRS1
IRS2
PPARG
MODY Diabetes
Mitochondrialer Diabetes mellitus
Neonataler Diabetes mellitus
Nichtinsulinabhängiger Diabetes mellitus 1
Pankreopriver Diabetes mellitus
Schwere Fettsucht mit Typ 2 Diabetes
Suszeptibilität für Typ 1 Diabetes 01

Referenzen:

1.

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2.

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3.

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4.

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5.

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6.

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7.

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8.

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9.

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10.

Baroni MG et al. (1999) A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease.

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11.

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12.

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13.

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14.

Hribal ML et al. (2000) The Gly-->Arg972 amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells.

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15.

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16.

Esposito DL et al. (2003) A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling.

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17.

Marini MA et al. (2003) The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients.

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18.

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19.

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20.

Federici M et al. (2004) G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells.

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21.

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22.

Perticone F et al. (2004) Impaired endothelial function in never-treated hypertensive subjects carrying the Arg972 polymorphism in the insulin receptor substrate-1 gene.

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23.

Kim JK et al. (2004) PKC-theta knockout mice are protected from fat-induced insulin resistance.

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24.

Taniguchi CM et al. (2005) Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism.

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25.

Sun XJ et al. (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein.

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26.

Wu A et al. (2008) Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes.

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27.

Shi B et al. (2007) Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells.

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28.

Zhang J et al. (2008) The cell growth suppressor, mir-126, targets IRS-1.

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29.

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30.

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31.

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32.

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33.

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35.

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36.

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37.

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38.

Araki E et al. (1993) Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization.

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39.

Almind K et al. (1996) A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies.

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40.

Esposito DL et al. (1996) Deletion of Gly723 in the insulin receptor substrate-1 of a patient with noninsulin-dependent diabetes mellitus.

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41.

Ogihara T et al. (1997) 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain.

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42.

Abe H et al. (1998) Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

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43.

RABSON SM et al. (1956) Familial hypertrophy of pineal body, hyperplasia of adrenal cortex and diabetes mellitus; report of 3 cases.

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44.

Moller DE et al. (1990) Functional properties of a naturally occurring Trp1200----Ser1200 mutation of the insulin receptor.

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45.

Shimada F et al. (1990) Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene.

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46.

Kadowaki T et al. (1990) Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding.

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47.

Yamamoto-Honda R et al. (1990) Phosphorylation state and biological function of a mutant human insulin receptor Val996.

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48.

Moller DE et al. (1988) Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (type A insulin resistance).

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49.

Klinkhamer MP et al. (1989) A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance.

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50.

Taira M et al. (1989) Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor.

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51.

Odawara M et al. (1989) Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.

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52.

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53.

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54.

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55.

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56.

Lander ES et al. (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children.

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57.

Kahn CR et al. (1988) The insulin receptor and the molecular mechanism of insulin action.

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58.

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59.

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60.

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61.

Moncada VY et al. (1986) Insulin-receptor biosynthesis in cultured lymphocytes from an insulin-resistant patient (Rabson-Mendenhall syndrome). Evidence for defect before insertion of receptor into plasma membrane.

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62.

Barnes ND et al. (1974) Insulin resistance, skin changes, and virilization: a recessively inherited syndrome possibly due to pineal gland dysfunction.

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63.

Taylor SI et al. (1983) Decreased insulin binding to cultured cells from a patient with the Rabson-Mendenhall syndrome: dichotomy between studies with cultured lymphocytes and cultured fibroblasts.

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64.

Terauchi Y et al. (2007) Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance.

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65.

Shimomura I et al. (2000) Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice.

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66.

Tobe K et al. (2001) Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2(-/-) mouse liver.

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67.

Uchida T et al. (2005) Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice.

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68.

Mammarella S et al. (2000) Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes.

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69.

Withers DJ et al. (1999) Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling.

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70.

Almind K et al. (1999) Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity.

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71.

Burks DJ et al. (2000) IRS-2 pathways integrate female reproduction and energy homeostasis.

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72.

Kubota N et al. (2000) Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia.

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73.

Wang H et al. (2001) New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.

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74.

Fritsche A et al. (2001) The prevalent Gly1057Asp polymorphism in the insulin receptor substrate-2 gene is not associated with impaired insulin secretion.

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75.

D'Alfonso R et al. (2003) Polymorphisms of the insulin receptor substrate-2 in patients with type 2 diabetes.

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76.

Lautier C et al. (2003) Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation.

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77.

Hennige AM et al. (2003) Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes.

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78.

Lin X et al. (2004) Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes.

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79.

Taguchi A et al. (2007) Brain IRS2 signaling coordinates life span and nutrient homeostasis.

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80.

Selman C et al. (2008) Comment on "Brain IRS2 signaling coordinates life span and nutrient homeostasis".

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81.

None (2008) A victory for PETA.

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82.

Sun XJ et al. (1995) Role of IRS-2 in insulin and cytokine signalling.

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83.

Withers DJ et al. (1998) Disruption of IRS-2 causes type 2 diabetes in mice.

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84.

Foti D et al. (2005) Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice.

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85.

Højlund K et al. (2004) A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene.

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86.

Kulkarni RN et al. (1999) Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes.

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87.

Michael MD et al. (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction.

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88.

Brüning JC et al. (2000) Role of brain insulin receptor in control of body weight and reproduction.

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89.

Brunetti A et al. (2001) Transcriptional regulation of human insulin receptor gene by the high-mobility group protein HMGI(Y).

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90.

Salmeen A et al. (2000) Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B.

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91.

Leibiger B et al. (2001) Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells.

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92.

Guerra C et al. (2001) Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance.

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93.

Rajala RV et al. (2001) Interaction of the insulin receptor beta-subunit with phosphatidylinositol 3-kinase in bovine ROS.

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94.

McCarthy LC et al. (2001) Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

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95.

Belke DD et al. (2002) Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression.

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96.

Longo N et al. (2002) Genotype-phenotype correlation in inherited severe insulin resistance.

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97.

Blüher M et al. (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance.

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98.

Blüher M et al. (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue.

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99.

Song J et al. (2003) Axons guided by insulin receptor in Drosophila visual system.

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100.

Maassen JA et al. (2003) Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance.

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101.

Cama A et al. (1992) Substitution of isoleucine for methionine at position 1153 in the beta-subunit of the human insulin receptor. A mutation that impairs receptor tyrosine kinase activity, receptor endocytosis, and insulin action.

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102.

Longo N et al. (1992) Reduced mRNA and a nonsense mutation in the insulin-receptor gene produce heritable severe insulin resistance.

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103.

Kitamura T et al. (2004) Mosaic analysis of insulin receptor function.

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104.

Savkur RS et al. (2004) Insulin receptor splicing alteration in myotonic dystrophy type 2.

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105.

Okamoto H et al. (2004) Transgenic rescue of insulin receptor-deficient mice.

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106.

Corl AB et al. (2005) Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster.

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107.

Benecke H et al. (1992) Alternatively spliced variants of the insulin receptor protein. Expression in normal and diabetic human tissues.

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108.

Barbetti F et al. (1992) Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis.

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109.

Cocozza S et al. (1992) NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene.

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110.

Shimada F et al. (1992) Abnormal messenger ribonucleic acid (mRNA) transcribed from a mutant insulin receptor gene in a patient with type A insulin resistance.

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111.

Kadowaki T et al. (1991) Substitution of arginine for histidine at position 209 in the alpha-subunit of the human insulin receptor. A mutation that impairs receptor dimerization and transport of receptors to the cell surface.

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112.

McKern NM et al. (2006) Structure of the insulin receptor ectodomain reveals a folded-over conformation.

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113.

van der Vorm ER et al. (1992) An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport.

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114.

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115.

Biddinger SB et al. (2008) Hepatic insulin resistance directly promotes formation of cholesterol gallstones.

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117.

Cama A et al. (1991) A mutation in the tyrosine kinase domain of the insulin receptor associated with insulin resistance in an obese woman.

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118.

Taylor SI et al. (1991) Genetic basis of endocrine disease. 1. Molecular genetics of insulin resistant diabetes mellitus.

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119.

Christiansen K et al. (1991) A model for the quaternary structure of human placental insulin receptor deduced from electron microscopy.

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120.

Kusari J et al. (1991) Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles.

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121.

Moller DE et al. (1990) A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance.

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122.

Williams JF et al. (1990) Characterization of an insulin receptor mutant lacking the subunit processing site.

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123.

Kadowaki T et al. (1990) A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction.

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124.

Menting JG et al. (2013) How insulin engages its primary binding site on the insulin receptor.

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125.

Kadowaki T et al. (1990) Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance.

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126.

Ojamaa K et al. (1988) Defects in human insulin receptor gene expression.

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127.

Shaw DJ et al. (1986) Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19.

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128.

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129.

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130.

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131.

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132.

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133.

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134.

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135.

Ward GM et al. (1986) Structure of the human erythrocyte insulin receptor.

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136.

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137.

Kittur D et al. (1987) Insulin binding to human B lymphoblasts is a function of HLA haplotype.

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138.

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139.

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140.

Tevaarwerk GJ et al. (1979) Studies on insulin resistance and insulin receptor binding in myotonia dystrophica.

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141.

Grunberger G et al. (1984) Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding.

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142.

Grigorescu F et al. (1984) Defect in insulin receptor phosphorylation in erythrocytes and fibroblasts associated with severe insulin resistance.

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143.

Williams DL et al. (1984) New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia.

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144.

Roth RA et al. (1983) Insulin receptor: evidence that it is a protein kinase.

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145.

Scarlett JA et al. (1982) Insulin resistance and diabetes due to a genetic defect in insulin receptors.

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146.

Ferrannini E et al. (1982) Impaired insulin degradation in a patient with insulin resistance and acanthosis nigricans.

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147.

Mariani S et al. (1982) Insulin resistance in a child with Acanthosis nigricans type A.

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148.

Wertheimer E et al. (1993) Homozygous deletion of the human insulin receptor gene results in leprechaunism.

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149.

Esposito L et al. (1995) Failure to detect Glut4-Ile383 and IR-Gln1152 variants in NIDDM (non-insulin dependent diabetes mellitus) and control subjects in an Italian population.

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150.

Hone J et al. (1994) Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance.

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151.

Cama A et al. (1993) Substitution of glutamic acid for alanine 1135 in the putative "catalytic loop" of the tyrosine kinase domain of the human insulin receptor. A mutation that impairs proteolytic processing into subunits and inhibits receptor tyrosine kinase activity.

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152.

Krook A et al. (1993) Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism.

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153.

van der Vorm ER et al. (1994) A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding.

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154.

Quon MJ et al. (1994) Tyrosine kinase-deficient mutant human insulin receptors (Met1153-->Ile) overexpressed in transfected rat adipose cells fail to mediate translocation of epitope-tagged GLUT4.

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155.

Moller DE et al. (1994) Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.

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156.

al-Gazali LI et al. (1993) A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents.

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157.

Longo N et al. (1993) Activation of glucose transport by a natural mutation in the human insulin receptor.

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158.

Elbein SC et al. (1993) Methionine for valine substitution in exon 17 of the insulin receptor gene in a pedigree with familial NIDDM.

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159.

Accili D et al. (1996) Early neonatal death in mice homozygous for a null allele of the insulin receptor gene.

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160.

Hart LM et al. (1996) Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: a population-based study.

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161.

Takahashi Y et al. (1998) Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Mendenhall's syndrome.

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162.

Brüning JC et al. (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance.

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163.

OMIM.ORG article

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164.

Wikipedia Artikel

Wikipedia DE (Insulinresistenz) external link
Update: 14. August 2020
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