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  • Lipoproteins  (2)
  • mutations  (2)
  • 1
    ISSN: 1432-0428
    Schlagwort(e): Keywords Hepatocyte nuclear factor-4α ; non-insulin-dependent diabetes mellitus ; insulin response ; mutations ; transcription factors.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Mutations in the hepatocyte nuclear factor-4α (HNF-4α) gene cause the type 1 form of maturity onset diabetes of the young (MODY1). To address the question of whether genetic variability of HNF-4α is associated with late onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of HNF-4α were identified: Thr/Ile130, which has been reported previously and a novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM patients and in none of 217 glucose tolerant control subjects; thus it cannot be excluded that this mutation may have an impact on NIDDM susceptibility. Among 509 NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7 % (95 % confidence interval: 3.4–6.0 %) compared to 1.9 % (0.7–3.1 %) among 239 control subjects (p = 0.008). However, in a population sample of 942 Swedish men with an average age of 70 years the allelic frequency of the variant was similar in 246 men with either impaired glucose tolerance (5.6 % [2.6–8.6 %]) or NIDDM (5.4 % [2.7–8.1 %]) as compared to 666 glucose tolerant men (5.1 % [3.9–6.3 %]). Also in a population sample of 369 young healthy Danes the prevalence of the codon 130 variant (4.7 % [3.2–6.2 %]) was similar to what was found in Swedish Caucasians. Thus, the allelic frequency of the Thr/Ile130 variant among the control subjects in the Danish case-control study deviates from the prevalence in the two other studies which is why we consider the significant association between the codon 130 variant and NIDDM an incidental finding. In glucose tolerant subjects the codon 130 variant in its heterozygous form had no major effect on glucose-induced insulin and C-peptide release although a tendency to a lower insulin secretion during an oral glucose tolerance test was seen in middle-aged subjects. In conclusion, variability in the coding region of the HNF-4α gene is not a common cause of NIDDM among whites of Danish ancestry. However, a Val/Met255 mutation was found exclusively in NIDDM patients (0.8 % of cases) and functional as well as family segregation studies are needed to determine whether this HNF-4α variant is a NIDDM causing mutation. [Diabetologia (1997) 40: 980–983]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin receptor substrate-2 ; mutations ; Type II diabetes ; insulin secretion ; insulin sensitivity.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aims/hypothesis. The aim of this study was to screen part of the putative promoter sequence in addition to 14 potential phosphotyrosine residues of human IRS-2 for genetic variability which might cause changes in protein expression or function. Furthermore, the potential impact on insulin secretion and sensitivity of a previously identified IRS-2 variant (Gly1057Asp) was analysed Methods. The screenings were carried out by the SSCP-heteroduplex technique on DNA from Type II (non-insulin-dependent) diabetic patients. The impact of the Gly1057Asp variant was analysed in four glucose-tolerant Scandinavian study groups. Results. The results showed no nucleotide substitutions in the promoter sequence, however, a novel heterozygous amino acid variant was identified (Leu647Val). In an association study, the new variant was found in 3 of 413 diabetic patients and in none of 280 glucose tolerant subjects. The variant did not affect the binding of IRS-2 to the insulin receptor or p85α of phosphatidylinositol 3-kinase when measured in the yeast two-hybrid system. Examination of the common Gly1057Asp variant in 363 young healthy subjects and in 228 glucose tolerant offspring of one diabetic parent showed no differences in insulin secretion or insulin sensivity after an intravenous glucose tolerance test. Glucose tolerant middle-aged subjects homozygous for the polymorphism (n = 31), however, had on average a 25 % decrease in fasting serum insulin concentrations (p = 0.009) and 28 % (p = 0.01) and 34 % (p = 0.003) reductions in serum insulin concentrations at 30 and 60 min, respectively, during an OGTT compared with wildtype carriers (n = 107). In a cohort of 639 elderly Swedish men the amino acid variant did not have any detectable impact on insulin secretion after an OGTT. Conclusion/interpretation. No genetic variability was found in the IRS-2 promoter. A rare IRS-2 variant at codon 647 has been identified in Type II diabetic patients. The prevalent codon 1057 polymorphism had no consistent effect on insulin secretion or insulin sensitivity. [Diabetologia (1999) 42: 1244–1249]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 19-22 
    ISSN: 1432-1041
    Schlagwort(e): Bisoprolol ; Lipoproteins ; Hypertension ; β-adrenoceptor antagonists
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of bisoprolol 2.5 and 5 mg per day on blood pressure, and lipoprotein and apolipoprotein concentrations were compared in 18 newly detected hypertensives in a double-blind, crossover study. All treatment results were related to the values at the end of a four-week placebo run-in period. Each of the two following treatment periods lasted for 3 months. The systolic and diastolic pressures in the supine position were reduced by 19.5/11.7 mm Hg and 14.6/10.4 mm Hg by 2.5 and 5 mg bisoprolol per day, respectively, with no significant difference in effect. Supine heart rate was reduced by 4.7 and 8.2 beats · min−1, respectively, (P=0.0517 for different effects). The cholesterol concentration in low-density (LDL) and high-density (HDL) lipoproteins was reduced during both regimens, by about 0.3 and 0.1 mmol·l−1, respectively, difference not significant. Triglyceride concentrations were not significantly affected during either regimen. We conclude that, in this study population, treatment with bisoprolol 2.5 mg per day was equally effective as 5.0 mg per day in reducing blood pressure. The effects on lipoprotein concentrations were small and included an unexpected reduction in LDL-cholesterol concentration. A low dose of a highly selective β-adrenoceptor blocker like bisoprolol appears to retain the blood pressure reducing capacity and has lost most of the unfavourable effects on lipoproteins characteristic of higher doses.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of applied physiology 52 (1984), S. 426-430 
    ISSN: 1439-6327
    Schlagwort(e): Apoproteins ; Lipoproteins ; Insulin ; Blood lactate ; Physical training
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Eight well-trained males were studied before, during and after 6 months of a progressively increased amount of endurance training in order to elucidate the effects on the apoproteins and apo-lipoproteins. Initially high HDL-cholesterol levels were revealed (1.62±0.15 mmol×l−1, mean ± SE.). After a transient but not significant, slight decline at the onset of the increased training program (1.57±0.06 mmol×l−1) HDL-cholesterol increased gradually to the end of the training period (1.92±0.12 mmol×l−1). There was an increased aerobic capacity as judged by maximal oxygen uptake and by lactate concentration during standardized submaximal work. However, at the end of the training period, a levelling off in maximal oxygen uptake was revealed, while HDL-cholesterol was still increasing. The present data demonstrate that HDL can be influenced by training at all levels of aerobic capacity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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