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Targeting the zinc transporter ZIP7 in the treatment of insulin resistance and type 2 diabetes

Citation

Adulcikas, J and Sonda, S and Norouzi, S and Sohal, SS and Myers, S, Targeting the zinc transporter ZIP7 in the treatment of insulin resistance and type 2 diabetes, Nutrients, 11, (2) pp. 1-15. ISSN 2072-6643 (2019) [Refereed Article]


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Copyright 2019 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3390/nu11020408

Abstract

Type 2 diabetes mellitus (T2DM) is a disease associated with dysfunctional metabolic processes that lead to abnormally high levels of blood glucose. Preceding the development of T2DM is insulin resistance (IR), a disorder associated with suppressed or delayed responses to insulin. The effects of this response are predominately mediated through aberrant cell signalling processes and compromised glucose uptake into peripheral tissue including adipose, liver and skeletal muscle. Moreover, a major factor considered to be the cause of IR is endoplasmic reticulum (ER) stress. This subcellular organelle plays a pivotal role in protein folding and processes that increase ER stress, leads to maladaptive responses that result in cell death. Recently, zinc and the proteins that transport this metal ion have been implicated in the ER stress response. Specifically, the ER-specific zinc transporter ZIP7, coined the "gate-keeper" of zinc release from the ER into the cytosol, was shown to be essential for maintaining ER homeostasis in intestinal epithelium and myeloid leukaemia cells. Moreover, ZIP7 controls essential cell signalling pathways similar to insulin and activates glucose uptake in skeletal muscle. Accordingly, ZIP7 may be essential for the control of ER localized zinc and mechanisms that disrupt this process may lead to ER-stress and contribute to IR. Accordingly, understanding the mechanisms of ZIP7 action in the context of IR may provide opportunities to develop novel therapeutic options to target this transporter in the treatment of IR and subsequent T2DM.

Item Details

Item Type:Refereed Article
Keywords:zinc, zinc transporters, ZIP7, insulin resistance, endoplasmic reticulum stress, type 2 diabetes
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Adulcikas, J (Mr John Adulcikas)
UTAS Author:Sonda, S (Dr Sabrina Sonda)
UTAS Author:Norouzi, S (Mrs Shaghayegh Norouzi)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
UTAS Author:Myers, S (Dr Stephen Myers)
ID Code:130852
Year Published:2019
Web of Science® Times Cited:16
Deposited By:Health Sciences
Deposited On:2019-02-18
Last Modified:2022-08-19
Downloads:33 View Download Statistics

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