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

Autor:	Per Bendix Jeppesen, Johan Palmfeldt, Anne Karina Christensen, Charlotte Christie Petersen, Jørgen Rungby, Kamille Smidt, Agnete Larsen, Birgitte Brock, Bent Honoré, Trine Maxel
Rok vydání:	2019
Předmět:	0301 basic medicine Proteomics LIVER MITOCHONDRIAL-DNA medicine.medical_treatment lcsh:Medicine Apoptosis 0302 clinical medicine Insulin-Secreting Cells Gene expression Insulin Secretion Hyperinsulinemia Glucose homeostasis Insulin RNA Small Interfering lcsh:Science ZNT8 Cation Transport Proteins Multidisciplinary Chemistry Diabetes PROLIFERATION ASSOCIATION Cell biology Mitochondria Up-Regulation Knockout mouse Insulin processing PROTEINS Cell Survival Down-Regulation Zinc Transporter 8 METABOLISM Article Cell Line 03 medical and health sciences Downregulation and upregulation medicine Gene silencing Animals Gene Silencing RNA Messenger IRON UPTAKE IDENTIFICATION lcsh:R Reproducibility of Results medicine.disease DIABETIC-PATIENTS Rats 030104 developmental biology Glucose Gene Expression Regulation lcsh:Q Metallothionein 030217 neurology & neurosurgery
Zdroj:	Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-15 (2019) Maxel, T, Smidt, K, Petersen, C C, Honoré, B, Christensen, A K, Jeppesen, P B, Brock, B, Rungby, J, Palmfeldt, J & Larsen, A 2019, ' The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function : Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells ', Scientific Reports, vol. 9, no. 1, 8589 . https://doi.org/10.1038/s41598-019-44954-1
ISSN:	2045-2322
DOI:	10.1038/s41598-019-44954-1
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3549fdbb388bee1a4ab6cf05f6cc1b0f https://pubmed.ncbi.nlm.nih.gov/31197210 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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