Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function: Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Direct exposure of the head to solar heat radiation impairs motor-cognitive performance

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Glycemic control and use of glucose-lowering medications in hospital-admitted type 2 diabetes patients over 80 years

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Lipidomic profiles, lipid trajectories and clinical biomarkers in female elite endurance athletes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: A randomised controlled trial

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Characteristics influencing expected cognitive performance during hypoglycaemia in type 2 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Antidiabetic medication and risk of dementia in patients with type 2 diabetes. A nested case-control study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Experimental non-severe hypoglycaemia substantially impairs cognitive function in type 2 diabetes: a randomised crossover trial

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Insulin secretion from pancreatic beta-cells is dependent on zinc ions as essential components of insulin crystals, zinc transporters are thus involved in the insulin secretory process. Zip14 (SLC39a14) is a zinc importing protein that has an important role in glucose homeostasis. Zip14 knockout mice display hyperinsulinemia and impaired insulin secretion in high glucose conditions. Endocrine roles for Zip14 have been established in adipocytes and hepatocytes, but not yet confirmed in beta-cells. In this study, we investigated the role of Zip14 in the INS-1E beta-cell line. Zip14 mRNA was upregulated during high glucose stimulation and Zip14 silencing led to increased intracellular insulin content. Large-scale proteomics showed that Zip14 silencing down-regulated ribosomal mitochondrial proteins, many metal-binding proteins, and others involved in oxidative phosphorylation and insulin secretion. Furthermore, proliferation marker Mki67 was down-regulated in Zip14 siRNA-treated cells. In conclusion, Zip14 gene expression is glucose sensitive and silencing of Zip14 directly affects insulin processing in INS-1E beta-cells. A link between Zip14 and ribosomal mitochondrial proteins suggests altered mitochondrial RNA translation, which could disturb mitochondrial function and thereby insulin secretion. This highlights a role for Zip14 in beta-cell functioning and suggests Zip14 as a future pharmacological target in the treatment of beta-cell dysfunction.

OriginalsprogEngelsk
Artikelnummer8589
TidsskriftScientific Reports
Vol/bind9
Udgave nummer1
Sider (fra-til)1-15
Antal sider15
ISSN2045-2322
DOI
StatusUdgivet - 13 jun. 2019

ID: 57397186