Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation

Abstract

Zinc is an essential micronutrient with diverse catalytic, structural, and regulatory roles across various life forms. Its essentiality for human health was recognized in the 1960s, but advancements in understanding the functions of zinc at the tissue, cell, and subcellular levels have accelerated, particularly with the identification of zinc transporters (ZNT). Zinc homeostasis is primarily facilitated by 2 families of transporters, the SLC30A/ZNT (ZNT) and SLC39A/Zrt-Irt-like proteins (ZIP). Among these, the ZNT family transporter ZNT8 has been well-studied for its involvement in insulin production, secretion, and the viability of pancreatic β cells. However, the roles of ZIP family transporters in β-cell insulin-related functions remain less explored. There have been studies implicating regulatory roles of ZIP4, ZIP5, ZIP6, and ZIP7 in β cells and emerging evidence for the involvement of ZIP8 and ZIP14 in β cell function. Despite these insights, the limited number of studies on ZIP family transporters highlights the need to consolidate existing literature to identify gaps and establish targeted, comprehensive research approaches that can further elucidate their critical roles in cellular zinc homeostasis and insulin metabolism. In this review, we first address the role of zinc in insulin production, secretion, and action. Second, we discuss the known ZIP transporters that potentially facilitate zinc delivery to specific cell compartments, focusing on literature addressing zinc and ZNT specifically relevant to insulin and glucose metabolism.

Keywords: ZIP14; ZIP8; diabetes; glucose metabolism; hyperinsulinemia.