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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 347-348 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 311-318 
    ISSN: 1432-0428
    Keywords: Guinea pig kidney ; insulin binding and degrading activity ; solubilization ; gel filtration ; isoelectric focusing ; concanavalin A-agarose affinity chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin binding and degrading activities were solubilized by a nonionic detergent. Triton X100, from guinea pig kidney particulate fractions (100,000 × g pellet). The solubilized insulin binding activity appeared as a single peak on Sepharose 6B gel filtration with a Stokes radius of 73 A. The pI of the solubilized insulin binding activity determined by flat-bed isoelectric focusing was 5.6. On the other hand, the Stokes radius of the solubilized molecule with insulin degrading activity was 54 Å by the same column with a pI of 5.2. More than 98% of the insulin binding activity could be adsorbed to a column of concanavalin A-agarose, while about 94% of the insulin degrading activity could not be adsorbed to this column. These results strongly suggest that the macromolecule for the insulin binding activity is not identical to that for the insulin degrading activity.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    ISSN: 1432-0428
    Keywords: Improvement of insulin response ; glucose tolerance test ; treatment of diabetes ; diet treatment ; sulphonylurea treatment ; insulin treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The changes in insulin response to a 100 g glucose tolerance test after treatment by diet, sulphonylurea and insulin were compared in non-ketotic diabetic patients who had fasting blood glucose concentrations higher than 160 mg/100 ml. Patients were selected so that their pre-treatment and post-treatment blood glucose levels were comparable between different treatment groups. Their insulin responses were poor initially but increased significantly when the diabetic state was improved by each treatment. The degree of improvement of insulin response was similar between different treatment groups, when their fasting blood glucose decreased below 140 mg/100 ml and the glucose tolerance curves were improved to a similar extent. Preand post-treatment ∑ IRI values (sum of insulin values during glucose tolerance test, mean±SD) were 102±50 and 200±37 μU/ml in diet-treated group (n = 28), 90±40 and 195±53 μU/ml in sulphonylurea-treated-group (n=48), and 83±28 and 193±38 μU/ml in insulin-treated group (n = 13), respectively. The data suggest that the poor insulin response in overt diabetes results not only from an inherent insensitivity of B-cells to glucose but also from the metabolic derangement of diabetes. Poor insulin response and overtly diabetic metabolism seems to form a vicious cycle.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1432-0428
    Keywords: Keywordsβ3-adrenergic receptor ; body mass index ; visceral obesity ; triglyceride ; lipolysis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Trp64Arg mutation of the β3-adrenergic receptor (β3AR) is prevalent in several ethnic groups and is associated with weight gain, and some features of syndrome X such as insulin resistance and dyslipidaemia. Nevertheless, it is not known at present whether this mutation is associated with visceral obesity, which is an important risk factor for the development of hypertension, dyslipidaemia, insulin resistance, non-insulin-dependent diabetes mellitus, and atherosclerosis. To investigate whether this mutation may contribute to visceral obesity, we studied the relationships between β3AR genotypes and clinical phenotypes. The Trp64Arg allele of β3AR was examined in 278 Japanese men with respect to variables relating to visceral obesity assessed by computerised tomography. To detect the Trp64Arg mutation, polymerase chain reaction-restriction fragment length polymorphism analysis using Bst NI digestion was performed. This mutation was more frequently observed in subjects with higher body mass index (BMI) (p = 0.02). Moreover, in 120 subjects with a moderate degree of obesity (22 M BMI 〈 26.4 kg/m2), the mutation (homozygotes and heterozygotes) was associated with visceral obesity (higher ratio of visceral to subcutaneous fat area; V/S) (p = 0.03). Furthermore, the Trp64Arg allele was more frequent in subjects with lower serum triglyceride levels (p = 0.02) and the Trp64Arg homozygotes, but not heterozygotes, exhibited lower triglyceride levels. Thus, this mutation appears to be associated with visceral obesity but with lower serum triglyceride. It is suggested that those with the mutation may describe a subset of subjects characterized by decreased lipolysis in visceral adipose tissue. [Diabetologia (1997) 40: 469–472]
    Type of Medium: Electronic Resource
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  • 7
    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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  • 8
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 154 (1988), S. 1204-1211 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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