Correlative imaging reveals metal dyshomeostasis and altered zinc coordination environments in a pre-clinical Type 2 diabetes model
Gaewyn Ellison, Arazu Sharif, Meg Willans, Ashley Hollings, Ryu Takechi, Keith Bambery, Valerie Mitchell, Daryl L Howard, Mark J Hackett
TL;DR
This study uses imaging techniques to show how zinc levels and coordination change in the pancreas of diabetic mice, revealing disruptions in zinc homeostasis linked to diabetes progression.
Contribution
The study introduces correlative imaging to explore zinc speciation and coordination in a pre-clinical diabetes model, revealing novel insights into zinc dyshomeostasis.
Findings
Zinc depletion in young diabetic islets correlates with reduced insulin and increased metallothionein expression.
Zinc speciation shifts from cysteine to histidine-like coordination in diabetic islets.
Older diabetic mice show normalized zinc levels despite altered protein ligand content.
Abstract
Zinc ions are highly abundant in pancreatic islet tissue, and multiple lines of evidence link loss of zinc homeostasis to poor glucose regulation in both type 1 and type 2 diabetes. Two major islet zinc-binding proteins, insulin and metallothionein, play crucial roles in beta cell function and glucose regulation. Here we used X-ray fluorescence microscopy (XFM) to map zinc and five additional elements (Cl, K, Ca, Fe, and Cu) to compare the metallome of exocrine, peri-islet and islet regions in young and old, non-diabetic control and diabetic (db/db) mice. We also determined the main forms of zinc found in pancreatic tissue using X-ray absorption near-edge structure (XANES) spectroscopic imaging. This allowed investigation of the relationship between zinc speciation and its protein ligands using correlative immunofluorescent imaging to assess whether zinc coordination may play a role in…
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Taxonomy
TopicsTrace Elements in Health · Plant Micronutrient Interactions and Effects · Pancreatic function and diabetes