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  • 1
    ISSN: 1432-0428
    Keywords: Spontaneously diabetic mice ; non-obese diabetic mice ; kidney glycosidase activities ; α- & β-glycosidase ; parabiosis ; diabetic control ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spontaneously diabetic non-obese mice of the ICR strain were newly inbred in Shionogi laboratory, Japan. Animals became diabetic suddenly, more frequently and severely in females. Blood glucose levels were 452±73 mg/100 ml with serum insulin levels of 〈 1.0 μU/ml in the fed state. Parabiosis with normal control ICR mice for 2 weeks decreased the blood glucose level to 260±51 mg/ 100ml (P〈0.01) and resulted in serum insulin levels of 46.0±18.0 μU/ml (P〈0.01). Kidney homogenate β-N-acetylglucosaminidase and β-galactosidase activities were reduced in diabetic mice (42% and 44% decrease respectively) (P〈0.025 and P〈0.001), and restored almost to normal after 2 weeks of parabiosis. Renal α-mannosidase activity was decreased 43% (P〈0.001) in the diabetic mice but unaffected by parabiosis. Serum β-N-acetylglucosaminidase, β-galactosidase and α-glucosidase activities were significantly increased in diabetic mice (179%; 233% and 58% increase respectively) (P〈0.005, P〈0.001 and P〈0.001), and returned to normal with parabiosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Gut glucagon ; depancreatized dogs ; insulin-induced hypoglycaemia ; arginine infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fasting (24 h) normal dogs and depancreatized dogs were injected intravenously with highly purified porcine insulin (Actrapid) in the doses of 0.2 U/kg and 0.5 U/kg, respectively. Blood glucose decreased from 152±41 (SEM) mg/100 ml to 39±7 mg/100 ml in the depancreatized dog and from 95±3 mg/100 ml to 42±4 mg/100 ml in the normal animal. Using a specific antiserum for “pancreatic” glucagon, the circulating level of glucagon immunoreactivity did not rise from the basal value of 247±31 pg/ml in the depancreatized group whereas it rose significantly from 223±24 pg/ml to 321±41 pg/ml in the normal group. In contrast intravenous infusion of 7 g of arginine increased “pancreatic” glucagon immunoreactivity in both groups. Thus, extrapancreatic glucagon of the pancreatic type does not respond to hypoglycaemia but to arginine infusion.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 1306-1312 
    ISSN: 1432-0428
    Keywords: Keywords Islets of Langerhans ; Fas ; CD95 ; apoptosis ; interleukin-1 ; interferon-γ ; DNA cleavage.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was conducted to investigate the possible involvement of Fas in β-cell death in insulitis of Type 1 (insulin-dependent) diabetes mellitus. Although primary cultured Balb/c mouse islet cells did not express Fas mRNA, 4–12 hours of treatment with 102-105 U/l of mouse interleukin-1 α (IL-1α) induced the expression of Fas mRNA. Surface Fas expression was detected by immunofluorescence flow cytometry using a non-cytolytic anti-Fas monoclonal antibody after 6 or 12 h of incubation with 103 U/l of IL-1α. Primary islet cells were resistant to an agonistic anti-Fas monoclonal antibody. However, 12 h pretreatment with IL-1α sensitized islet cells to its cytolytic effect. Significant cell death was observed 24 h after the addition of anti-Fas, and progressively increased until 72 h, when specific 51Cr release was 72 ± 6 %. Agarose gel electrophoresis of DNA extracted from cells exposed to IL-1α and agonistic anti-Fas showed internucleosomal DNA fragmentation, a hallmark of apoptotic cell death. Since the Fas antibody showed no cross-reactive activity of tumour necrosis factor (TNF), the cytotoxic effect was not mediated by TNF receptors. A protein synthesis inhibitor cycloheximide augmented Fas-mediated islet cell death. The Fas-mediated killing of islet cells was not l-arginine-dependent, or blocked by NG-monomethyl-l-arginine. β-TC1 cells also expressed Fas mRNA when exposed to IL-1α or IL-1α plus interferon-γ. These observations suggest that Fas-mediated apoptosis may be a mechanism of islet cell death in autoimmune insulitis. [Diabetologia (1996) 39: 1306–1312]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywordsβ2-adrenergic receptor gene ; polymorphism ; obesity ; triglyceride ; Type II diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess the role of polymorphisms in the β2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we analysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese subjects (body mass index 〈 27 kg/m2) and 108 obese subjects (body mass index ≥ 27 kg/m2). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.14, 95 % confidence interval 1.35–3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-dependent) diabetes mellitus than non-diabetic subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.13, 95 % confidence interval 1.34–3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesting that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum triglyceride than obese subjects homozygous for the wild type allele (2.68 ± 1.90 vs 1.18 ± 1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly16 homozygotes was lower in obese women when compared with non-obese women (11 % vs 28 %, p = 0.01, odds ratio 0.30, 95 % confidence interval 0.12–0.75), although the association was not present in male subjects. Thr164Ile substitution was not detected in the subjects of this study. These observations suggest that the amino-terminal polymorphisms of the β2-adrenergic receptor gene could be involved in the molecular pathogenesis of obesity and hypertriglyceridaemia, and thereby the development of Type II diabetes mellitus. [Diabetologia (1999) 42: 98–101]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Insulin promoter factor 1 ; polymorphism ; mutation ; insulin-dependency.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35 %) and lower in NIDDM patients (17 %) than in normal control subjects (28 %, p = 0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene. [Diabetologia (1998) 41: 603–605]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords Fatty acid-binding protein 2 ; intestinal fatty acid binding protein ; insulin resistance ; visceral fat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index of 24.4 ± 3.0 kg/m2. The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40: 706–710]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Serotonin, 5-HT2C receptor, promoter, polymorphism, obesity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Polymorphisms in the upstream region of the 5-HT2C receptor gene could play a part in the development of obesity.¶Methods. We screened the upstream region from 27 men by the single strand conformational polymorphism analysis and PCR-direct sequencing and then genotyped 466 non-obese (body mass index 〈 28 kg/m2) and 123 obese ( ≥ 28 kg/m2) men including 138 patients with Type II (non-insulin-dependent) diabetes mellitus.¶Results. Three loci of single nucleotide substitution (G→A at –995, C→T at –759, G→C at –697) and a (GT)n dinucleotide repeat polymorphism at –1,027 were identified. The frequency of –995/–759 and –697 variants was higher in non-obese subjects and that of –995/–759 variants in non-diabetic subjects. In the dinucleotide repeat locus, five alleles were detected including Z containing 17 repeats. The Z−6 allele was more common in non-obese subjects and the Z + 2 allele in obese subjects. Haplotype 3 (Z−6, –995A, –759T, –697C) was associated with leanness (p = 0.02) and the absence of diabetes (p = 0.033) and haplotype 9 (Z + 2, –995G, –759C, –697G) with obesity (p = 0.007). Haplotype 2 (Z−6, –995G, –759C, –697C) tended to be more common in non-obese subjects. A luciferase reporter assay showed that haplotype 2 and haplotype 3 had 1.44- or 2.58-fold higher promoter activities than the most common haplotype 6 (Z, –995G, –759C, –697G).¶Conclusion/interpretation. The haplotypes containing the nucleotide substitutions could be associated with higher transcription levels of the gene and thereby with resistance to obesity and Type II diabetes. Promoter polymorphisms of the 5-HT2C receptor gene may play an important part in genetic predisposition to the disorders. [Diabetologia (2000) 43: 373–376]
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 41 (1998), S. 125-125 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Materials science forum Vol. 304-306 (Feb. 1999), p. 367-372 
    ISSN: 1662-9752
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 197 (1993), S. 22-27 
    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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