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  • 2-deoxyglucose uptake  (1)
  • Keywords Insulin resistance syndrome  (1)
  • Type 2 (non-insulin-dependent) diabetes mellitus  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 19 (1980), S. 468-474 
    ISSN: 1432-0428
    Keywords: High glucose diet ; insulin receptor ; 2-deoxyglucose uptake ; glucose oxidation ; insulin sensitivity ; insulin responsiveness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To elucidate the mechanisms whereby changes in dietary composition affect the action of insulin on glucose metabolism, insulin binding and glucose uptake and oxidation have been studied in epididymal fat pad adipocytes from rats fed high glucose diets for 5 and 10 days. After 5 days, insulin binding was increased, due mainly to an increased number of receptors (3.4×105 vs. 2.4×105 sites per cell) in spite of increased plasma insulin levels (3.0±0.2 vs. 2.1±0.1 μg/l; p〈0.05). The maximal response of glucose oxidation to insulin was increased (925±55 vs. 510±58 n moles/2×105 cells/2h; p〈0.01) and the dose-response curve of glucose uptake was shifted to the left. After 10 days, receptor number decreased to the control level and the effect of insulin on glucose uptake and oxidation (% basal) were similar to controls. Thus, in the early stage of high glucose feeding, insulin receptor number, insulin sensitivity of glucose uptake, and insulin responsiveness of glucose oxidation were increased.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Hyperinsulinaemia ; tyrosine kinase activity ; Type 2 (non-insulin-dependent) diabetes mellitus ; obesity ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We analyzed single-stranded conformational poly morphisms to screen for mutations and polymorphisms in the insulin receptor gene in subjects with or without insulin resistance. Using this new technique, we demonstrated the existence of mutations in the insulin receptor gene which we had identified previously. In addition, a new mutation was found in exon 20 of the insulin receptor gene in a patient with moderate insulin resistance associated with morbid obesity, acanthosis nigricans, and polycystic ovary syndrome. The patient was heterozygous for a mutation substituting Leu (CTG) for Pro (CCG) at codon 1178. Pro1178 is a part of a characteristic sequence motif (D1150 F1151 G1152-A1177 P1178 E1179) common to many protein kinases. Analysis of single-stranded conformational polymorphisms was also used to estimate the frequency of a polymorphism at codon 1058. The two codons CAC (1058 His) and CAT (1058 His) both had a prevalence of 50% in 30 Japanese subjects. These data demonstrate that analysis of single-stranded conformational polymorphisms is a simple and sensitive screening method for mutations and polymorphisms in the insulin receptor gene in subjects with or without insulin resistance. Identification of a mutation in the insulin receptor gene in a patient with a moderate degree of insulin resistance associated with morbid obesity suggests that insulin receptor mutations may exist in patients with Type 2 (non-insulin-dependent) diabetes mellitus associated with a moderate degree of insulin resistance.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance syndrome ; mutation ; genotype ; phenotype ; tyrosine kinase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report a homozygous missense mutation at position 1092 (substitution of glutamine for arginine) in the tyrosine kinase domain of the insulin receptor in a patient with leprechaunism associated with severe insulin resistance and intrauterine growth retardation. Site-directed mutagenesis as well as analyses of the patient's lymphocytes revealed that this mutation causes a marked decrease in tyrosine kinase activity of the insulin receptor without any defect in insulin binding, which causes severe defects in insulin-stimulated glucose transport, glycogen synthesis and DNA synthesis. Thus, this is the first homozygous mutation resulting in a selective-kinase defect of the insulin receptor. Interestingly, the parents who are cousins and are heterozygous for the mutation have type A insulin resistance syndrome. This correlation between genotype and phenotype in a single pedigree suggests that the severity of the mutation will determine the phenotype. Based upon this assumption, we have been successful in prenatal diagnosis of the fifth child. Furthermore, we have demonstrated the effectiveness of clinical administration of insulin-like growth factor-I (IGF-I) in this patient and in vitro analysis of the patient's skin fibroblasts, suggesting that IGF-I can compensate for insulin action via the IGF-I receptor in a patient almost lacking functional insulin receptors. [Diabetologia (1997) 40: 412–420]
    Type of Medium: Electronic Resource
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