Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes.
A finely tuned subcellular distribution of zinc (Zn), through the coordinated action of Zn transporters (ZnTs) and metallothioneins (MTs), is crucial for optimal cell function. Dysfunctions of these proteins might act as key causative or promoting factors in several chronic pathologies. Evidence of their involvement in the pathogenesis of type 2 diabetes (DM2) is emerging. The association of single nucleotide polymorphisms in genes encoding ZnT-8 and MT with DM2 has drawn attention to the relevance of Zn homeostasis for insulin secretory capacity and responsiveness. Here, we propose that potential mechanisms leading to altered subcellular Zn distribution rather than deficiency might be important in DM2. Increasing knowledge of the mechanisms of Zn homeostasis and signalling should promote the development of targeted interventions with the potential to reduce the burden of disease.
Mocchegiani
Eugenio
E
Laboratory of Nutrigenomic and Immunosenescence, Research Department INRCA, Via Birarelli 8, 60121 Ancona, Italy. e.mocchegiani@inrca.it
Giacconi
Robertina
R
Malavolta
Marco
M
D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D015032:Zinc / Q000378:metabolism* / Q000502:physiology; D000075703:Zinc Transporter 8
D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D008668:Metallothionein; D015032:Zinc