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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Lear, PV, et al.
(författare)
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Des-acyl ghrelin has specific binding sites and different metabolic effects from ghrelin in cardiomyocytes
- 2010
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 151:7, s. 3286-3298
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Tidskriftsartikel (refereegranskat)abstract
- The current study aimed to compare the effects of the peptide hormone ghrelin and des-G, its unacylated isoform, on glucose and fatty acid uptake and to identify des-G-specific binding sites in cardiomyocytes. In the murine HL-1 adult cardiomyocyte line, ghrelin and des-G had opposing metabolic effects: des-G increased medium-chain fatty acid uptake (BODIPY fluorescence intensity), whereas neither ghrelin alone nor in combination with des-G did so. Ghrelin inhibited the increase in glucose uptake normally induced by insulin (rate of 2-[3H]deoxy-d-glucose incorporation), but des-G did not; des-G was also able to partially reverse the inhibitory effect of ghrelin. In HL-1 cells and primary cultures of neonatal rat cardiomyocytes, des-G but not ghrelin increased insulin-induced translocation of glucose transporter-4 from nuclear to cytoplasmic compartments (immunohistochemistry and quantitative confocal analysis). AKT was phosphorylated by insulin but not affected by ghrelin or des-G, whereas neither AMP-activated protein kinase nor phosphatase and tensin homolog deleted from chromosome 10 was phosphorylated by any treatments. HL-1 and primary-cultured mouse and rat cardiomyocytes each possessed two independent specific binding sites for des-G not recognized by ghrelin (radioreceptor assays). Neither ghrelin nor des-G affected viability (dimethylthiazol diphenyltetrazolium bromide assays), whereas both isoforms were equally protective against apoptosis. Therefore, in cardiomyocytes, des-G binds to specific receptors and has effects on glucose and medium-chain fatty acid uptake that are distinct from those of ghrelin. Real-time PCR indicated that expression levels of ghrelin O-acyltransferase RNA were comparable between HL-1 cells, human myocardial tissue, and human and murine stomach tissue, indicating the possibility of des-G conversion to ghrelin within our model.
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- Monroy-Iglesias, MJ, et al.
(författare)
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Serum Total Bilirubin and Risk of Cancer: A Swedish Cohort Study and Meta-Analysis
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- Bilirubin has strong antioxidant properties that have been hypothesized to be preventive against the development of cancer. Thus, we aimed to investigate the association between serum total bilirubin (STB) and risk of overall and site-specific cancers in the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort. We also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung). We found no association between high levels of STB and risk of overall cancer. Regarding site-specific cancer, there was an inverse association between increased STB and lung cancer (Hazard Ratio (HR) for the 4th quartile (Q4) vs. Q1: 0.50; 95%CI: 0.44–0.59) and gynecological cancer (HR for Q4 vs. Q1: 0.86; 95%CI: 0.76–0.99). A positive association was found with melanoma (HR for Q4 vs. Q1: 1.25; 95%CI: 1.06–1.47) and breast cancer (HR for Q4 vs. Q1: 1.13; 95%CI: 1.01–1.25) risk. The meta-analysis showed an inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.69; 95%CI: 0.55–0.86). No associations were seen for colorectal and breast cancer risk. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target.
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