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Sökning: WFRF:(Nassar N)

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  • Zhang, Q., et al. (författare)
  • Na+ current properties in islet alpha- and beta-cells reflect cell-specific Scn3a and Scn9a expression
  • 2014
  • Ingår i: Journal of Physiology-London. - 0022-3751. ; 592:21, s. 4677-4696
  • Tidskriftsartikel (refereegranskat)abstract
    • - and -cells express both Na(v)1.3 and Na(v)1.7 Na+ channels but in different relative amounts. The differential expression explains the different properties of Na+ currents in - and -cells. Na(v)1.3 is the functionally important Na+ channel subunit in both - and -cells. Islet Na(v)1.7 channels are locked in an inactive state due to an islet cell-specific factor. Mouse pancreatic - and -cells are equipped with voltage-gated Na+ currents that inactivate over widely different membrane potentials (half-maximal inactivation (V-0.5) at -100mV and -50mV in - and -cells, respectively). Single-cell PCR analyses show that both - and -cells have Na(v)1.3 (Scn3) and Na(v)1.7 (Scn9a) subunits, but their relative proportions differ: -cells principally express Na(v)1.7 and -cells Na(v)1.3. In -cells, genetically ablating Scn3a reduces the Na+ current by 80%. In -cells, knockout of Scn9a lowers the Na+ current by >85%, unveiling a small Scn3a-dependent component. Glucagon and insulin secretion are inhibited in Scn3a(-/-) islets but unaffected in Scn9a-deficient islets. Thus, Na(v)1.3 is the functionally important Na+ channel subunit in both - and -cells because Na(v)1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Na(v)1.7 sequence in brain and islets is identical and yet the V-0.5 for inactivation is >30mV more negative in -cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation.
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  • Gielen, Marij, et al. (författare)
  • Body mass index is negatively associated with telomere length : A collaborative cross-sectional meta-analysis of 87 observational studies
  • 2018
  • Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165. ; 108:3, s. 453-475
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
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  • Resultat 1-10 av 11
  • [1]2Nästa

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