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

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The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function : Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells. / Maxel, Trine; Smidt, Kamille; Petersen, Charlotte C; Honoré, Bent; Christensen, Anne K; Jeppesen, Per B; Brock, Birgitte; Rungby, Jørgen; Palmfeldt, Johan; Larsen, Agnete.

In: Scientific Reports, Vol. 9, No. 1, 13.06.2019, p. 8589.

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@article{237636ebcd8748cc898fb7bdd914acff,
title = "The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function: Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells",
abstract = "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.",
author = "Trine Maxel and Kamille Smidt and Petersen, {Charlotte C} and Bent Honor{\'e} and Christensen, {Anne K} and Jeppesen, {Per B} and Birgitte Brock and J{\o}rgen Rungby and Johan Palmfeldt and Agnete Larsen",
year = "2019",
month = "6",
day = "13",
doi = "10.1038/s41598-019-44954-1",
language = "English",
volume = "9",
pages = "8589",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function

T2 - Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells

AU - Maxel, Trine

AU - Smidt, Kamille

AU - Petersen, Charlotte C

AU - Honoré, Bent

AU - Christensen, Anne K

AU - Jeppesen, Per B

AU - Brock, Birgitte

AU - Rungby, Jørgen

AU - Palmfeldt, Johan

AU - Larsen, Agnete

PY - 2019/6/13

Y1 - 2019/6/13

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-44954-1

DO - 10.1038/s41598-019-44954-1

M3 - Journal article

VL - 9

SP - 8589

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -