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Updated: May 22, 2026

Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Regulation and functional effects of ZNT8 in human pancreatic islets
Bruno Lefebvre1, Brigitte Vandewalle, Anne-Sophie Balavoine
1Univ Lille Nord de France, F-59000 Lille, France. bruno.lefebvre@inserm.fr
Abstract:
Zinc ions are essential for the formation of insulin crystals in pancreatic β cells, thereby contributing to packaging efficiency of stored insulin. Zinc fluxes are regulated through the SLC30A (zinc transporter, ZNT) family. Here, we investigated the effect of metabolic stress associated with the prediabetic state (zinc depletion, glucotoxicity, and lipotoxicity) on ZNT expression and human pancreatic islet function. Both zinc depletion and lipotoxicity (but not glucotoxicity) downregulated ZNT8 (SLC30A8) expression and altered the glucose-stimulated insulin secretion index (GSIS). ZNT8 overexpression in human islets protected them from the decrease in GSIS induced by tetrakis-(2-pyridylmethyl) ethylenediamine and palmitate but not from cell death. In addition, zinc supplementation decreased palmitate-induced human islet cell death without restoring GSIS. Altogether, we showed that ZNT8 expression responds to variation in zinc and lipid levels in human β cells, with repercussions on insulin secretion. Prospects for increasing ZNT8 expression and/or activity may prove beneficial in type 2 diabetes in humans.
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