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The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn2+ levels
P. Dzianová, S. Asai, M. Chrudinová, L. Kosinová, P. Potalitsyn, P. Šácha, R. Hadravová, I. Selicharová, J. Kříž, JP. Turkenburg, AM. Brzozowski, J. Jiráček, L. Žáková
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
MR/R009066/1
Medical Research Council - United Kingdom
MR/K000179/1
Medical Research Council - United Kingdom
MR/R009066/1
Medical Research Council - United Kingdom
NV16-28249A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
NLK
Directory of Open Access Journals
od 2011
Free Medical Journals
od 2011
Freely Accessible Science Journals
od 2011-09-01
PubMed Central
od 2011
Europe PubMed Central
od 2011
Open Access Digital Library
od 2011-01-01
Open Access Digital Library
od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2011
PubMed
33081637
DOI
10.1098/rsob.200137
Knihovny.cz E-zdroje
- MeSH
- beta-buňky metabolismus ultrastruktura MeSH
- chemická frakcionace MeSH
- cytoplazmatická granula metabolismus MeSH
- exprese genu * MeSH
- glukosa metabolismus MeSH
- inzulin genetika metabolismus MeSH
- krysa rodu rattus MeSH
- Langerhansovy ostrůvky metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- průtoková cytometrie metody MeSH
- zinek metabolismus MeSH
- zinkový transportér 8 MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn2+-stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage.
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- $a Dzianová, Petra $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 116 10 Prague 6, Czech Republic
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- $a The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn2+ levels / $c P. Dzianová, S. Asai, M. Chrudinová, L. Kosinová, P. Potalitsyn, P. Šácha, R. Hadravová, I. Selicharová, J. Kříž, JP. Turkenburg, AM. Brzozowski, J. Jiráček, L. Žáková
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- $a Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn2+-stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage.
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