Zinc and Zinc Transporter Regulation in Pancreatic Islets and the Potential Role of Zinc in Islet Transplantation

Bosco, Mariea Dencey; Mohanasundaram, Daisy; Drogemuller, Chris; Lang, Carol J.; Zalewski, Peter D.; Coates, P. Toby

doi:10.1900/rds.2010.7.263

Cited by 31 publications

(24 citation statements)

References 105 publications

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“…A trivial explanation for our findings is that the lower-granularity population of cells represents non-β islet cells that can harbor Zn + granules (Bosco et al, 2010). However, the same two populations of β cells were identified in GFP + β cells from NOD mice, in which GFP was driven by Ins1 promoter.…”

Section: Discussionmentioning

confidence: 92%

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice

et al. 2017

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SUMMARY Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclophosphamide. Human β cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long-term survival of β cells in some patients.

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Section: Discussionmentioning

confidence: 92%

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice

et al. 2017

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“…ZnT3 (SLC30A3) protein has been reported in the islets, and in the pancreatic β cell line INS-1E but not in a corresponding pancreatic α-cell line, α-TC6 [40][41][42]. While ZnT3 mRNA was reported in purified human β cells in one study [38], levels were zero, or at the limit of detection, in samples from several subjects in another [37].…”

Section: Znt Familymentioning

confidence: 95%

Zinc and diabetes

Chabosseau

Rutter

2016

Archives of Biochemistry and Biophysics

154

104

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Zn 2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn 2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions. Abbreviation ISG: Insulin Secreting Granules; T2D: Type 2 Diabetes; T1D: Type 1 Diabetes; 2 Diabetes mellitus is a common metabolic disease, affecting approximately 9% of the adult population worldwide. It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].These early studies, as well as much more recent findings showing association between T2D risk and the inheritance of gene variants encoding a critical β cell Zn 2+ transporter, ZnT8[5] have generated considerable interest in the role of Zn 2+ in diabetes aetiology and as a possible therapeutic target [6]. Zinc and the diabetic patientScott and Fisher were the first to report a direct link between zinc and diabetes in patients.While assessing the insulin content in the pancreas of diabetic patients compared to nondiabetic cadavers, they showed that in the former group zinc content was reduced by 75 % [7].Epidemiological studies also demonstrated that diabetes and whole body zinc status are associated [8][9][10][11]. In T1D and T2D patients, serum zinc levels are significantly decreased [9][10][11], this being associated with an increased zinc urinary loss [8].Zinc may have important anti-oxidant properties, as it acts as a cofactor of the superoxide dismutase enzyme which regulates the detoxification of reactive oxygen species, regulating the expression and protecting against the oxidative stress induced by chronic hyperglycaemia (for review, [12]). Furthermore, zinc inhibits alpha-ketoglutarate-dependent mitochondrial respiration suggesting that Zn 2+ can interfere with mitochondrial antioxidant production and may also stimulate production of reactive oxygen [13].Zinc supplementation h...

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“…The concentration of Zn in these vesicles is very high, approximately 20 mM. Within the beta-cell secretory vesicles insulin and zinc form hexameric insulin crystal that contains two Zn atoms and six insulin molecules [12]. Although Zn is an essential trace metal, the intracellular Zn concentration is tightly regulated.…”

Section: Unique Zincmentioning

confidence: 99%

“…Inside the cell numerous metallothioneins buffer the Zn concentration [14]. In the human pancreatic islet can be identified 19 of the 24 known mammalian zinc transporters [12].…”

Section: Unique Zincmentioning

confidence: 99%

Type 1 diabetes epidemic in Finland is triggered by zinc-containing amorphous silica nanoparticles

Junnila¹

2015

Medical Hypotheses

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Zinc and Zinc Transporter Regulation in Pancreatic Islets and the Potential Role of Zinc in Islet Transplantation

Cited by 31 publications

References 105 publications

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice

Zinc and diabetes

Type 1 diabetes epidemic in Finland is triggered by zinc-containing amorphous silica nanoparticles

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