In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion
Open accessAbstract
Insulin-secreting pancreatic beta cells are exceptionally rich in zinc. In these cells, zinc is required for zinc-insulin crystallization within secretory vesicles. Secreted zinc has also been proposed to be a paracrine and autocrine modulator of glucagon and insulin secretion in pancreatic alpha and beta cells, respectively. However, little is known about the molecular mechanisms underlying zinc accumulation in insulin-containing vesicles. We previously identified a pancreas-specific zinc transporter, ZnT-8, which colocalized with insulin in cultured beta cells. In this paper we studied its localization in human pancreatic islet cells, and its effect on cellular zinc content and insulin secretion. In human pancreatic islet cells, ZnT-8 was exclusively expressed in insulin-producing beta cells, and colocalized with insulin in these cells. ZnT-8 overexpression stimulated zinc accumulation and increased total intracellular zinc in insulin-secreting INS-1E cells. Furthermore, ZnT-8-overexpressing cells display enhanced glucose-stimulated insulin secretion compared with control cells, only for a high glucose challenge, i.e. >10 mM glucose. Altogether, these data strongly suggest that the zinc transporter ZnT-8 is a key protein for both zinc accumulation and regulation of insulin secretion in pancreatic beta cells.
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Zn2+ uptake into insulin granules is mediated by the ZnT8 transporter.
“Zn2+ uptake into the insulin granules is mediated by the ZnT8 (Slc30a8/SLC30A8) transporter (117).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [117]
The Discussion says the results strongly suggest that ZnT8 enhances zinc storage in insulin granules and that its membrane topology is consistent with transport from the cytoplasm into insulin-containing vesicles. Those passages support a role for ZnT8, but present granule uptake as an inference rather than establishing the unqualified claim that ZnT8 mediates it. (LLM, conf=0.85)
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A genome-wide association study identifies novel risk loci for type 2 diabetes
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A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
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- Authors
- Chimienti, F., Devergnas, S., Pattou, F., Schuit, F., Garcia-Cuenca, R., Vandewalle, B., Kerr-Conte, J., Van Lommel, L., Grunwald, D., Favier, A., & Seve, M.
- Affiliations
- Université Joseph Fourier (FR)
- DRFMC/SCIB/LAN, UMR-E3 CEA/UJF, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble CEDEX 9, France
- Thérapie Cellulaire du Diabète, INSERM ERIT-M 0106 Faculté de Médecine, Place de Verdun, 59045 Lille, France
- KU Leuven (BE)
- Mellitech (France) (FR)
- Inserm (FR)
- Gene Expression Unit, Division of Biochemistry, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
- Laboratoire Canaux Ioniques et Signalisation, DRDC/LCI, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble CEDEX 9, France
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2006-10-15
- Volume
- 119
- Issue
- 20
- Pages
- 4199-4206
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2137761662
- Cited by
- 349
- References
- 1
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 6 · 2022: 7 · 2021: 14 · 2020: 11 · 2019: 21 · 2018: 15 · 2017: 18 · 2016: 20 · 2015: 24 · 2014: 23 · 2013: 19 · 2012: 33
- FWCI
- 18.81
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- zinc transporter 8, zinc transporters, zinc accumulation, insulin secretion, pancreatic beta cells, glucose-stimulated insulin secretion, secretory vesicles, pancreatic islets, INS-1E cells, zinc homeostasis
- MeSH terms
- Zinc Transporter 8, Insulin Secretion, Animals, Biological Transport, Cell Line, Cell Membrane, Cell Survival, Dose-Response Relationship, Drug, Glucagon, Glucose, HeLa Cells, Humans, Insulin, Islets of Langerhans, Male, Microscopy, Fluorescence, Models, Biological, Recombinant Fusion Proteins, Zinc, Gene Expression, Microscopy, Confocal, Secretory Vesicles, Cation Transport Proteins, Green Fluorescent Proteins, Insulin-Secreting Cells, Mice
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