The Zinc Transporter Zip14 (SLC39a14) Affects Beta-cell Function: Proteomics, Gene Expression, and Insulin Secretion Studies in INS-1E Cells

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jun 15

PMID 31197210

Citations 10

Authors

Trine Maxel

Kamille Smidt

Charlotte C Petersen

Bent Honore

Anne K Christensen

Per B Jeppesen

Birgitte Brock

Jorgen Rungby

Johan Palmfeldt

Agnete Larsen

Affiliations

Soon will be listed here.

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.

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