Zinc, pancreatic islet cell function and diabetes: new insights into an old story

Chimienti, Fabrice

doi:10.1017/s0954422412000212

Cited by 106 publications

(80 citation statements)

References 114 publications

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“…249 ZraP has been shown to bind zinc, 250 and a metalloproteomic study demonstrated that in zinc excess conditions, the large majority of cellular zinc in E. coli was bound to ZraP. 251 The catalytic molecular chaperone activity of ZraP is Zn-dependent, and Zn also affects its oligomerisation state, with higher oligomers (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) observed in the presence of zinc. A structure for ZraP from Salmonella typhimurium is available, but without bound Zn (pdb 3lay; Fig.…”

Section: View Article Onlinementioning

confidence: 99%

Advances in the molecular understanding of biological zinc transport

Blindauer

2015

Chem. Commun.

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Between 5 and 10% of all proteins of a given organism are estimated to require zinc for function, and hence zinc is essential for almost any given metabolic process. It is therefore of great interest to understand major players and mechanisms that ensure the tight and correct control of zinc distribution and speciation in organisms and their individual cells. Significant progress has been made in recent years regarding 3-dimensional structures and modes of action of zinc sensor proteins, membrane-bound zinc transporters for cellular and sub-cellular uptake and efflux, as well as intracellular binding proteins. This feature article highlights advances in structures, zinc-binding sites and thermodynamics of proteins that are involved in zinc homeostasis and trafficking, including developments in understanding the metal selectivity of proteins.

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Section: View Article Onlinementioning

confidence: 99%

Advances in the molecular understanding of biological zinc transport

Blindauer

2015

Chem. Commun.

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“…Copper, zinc, and selenium are cofactors of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and therefore play a pivotal role in the mechanism of cellular antioxidant defense [8]. Zinc has a pivotal role in the antioxidant system and also takes part in the synthesis, storage, and release of insulin [9]. The lower zinc levels have been associated with insulin resistance and chronic inflammation [10].…”

Section: Introductionmentioning

confidence: 99%

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism

Aydoğdu

Haymana

Soykut

et al. 2015

Biol Trace Elem Res

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Cardiometabolic diseases are prevalent in hypogonadism. The pathophysiologic mechanism of increased cardiometabolic risk in hypogonadal patients is not clear. Recently, trace elements have been linked to the development of chronic disease especially cardiovascular disease. We investigated the trace element levels in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and also searched for the relationship with metabolic risk factors. A total of 89 patients with CHH (mean age 21.8 ± 2.0 years) and 80 healthy control subjects (mean age 21.3 ± 1.1 years) were enrolled. The demographic parameters, homeostatic model assessment of insulin resistance (HOMA-IR) levels and plasma zinc, copper, and selenium levels, were measured in patients and healthy controls. The patients had higher waist circumferences (p = 0.014), triglyceride (p = 0.04), insulin (p = 0.004), HOMA-IR levels (p = 0.001), and lower selenium (p = 0.049), zinc (p = 0.004), and copper (p = 0.012) levels when compared to the healthy controls. There was a significant relationship between zinc levels and HOMA-IR levels (p = 0.015). In the regression analysis, zinc levels were independently associated with the calculated HOMA-IR levels (p = 0.015). The results of the present study show that plasma selenium, zinc, and copper levels are decreased in patients with CHH. Also, plasma zinc levels are independently associated with insulin resistance in patients with hypogonadism. Long-term follow-up studies are warranted to investigate the effect of trace elements on the increased cardiometabolic risk in hypogonadism.

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“…Zinc dyshomeostasis was associated with Alzheimer's disease and altered deposition of extracellular amyloid-b plaques (Craddock et al 2012). Decreased zinc content was also described in post-mortem pancreata of diabetic individuals over 75 years ago (Scott and Fisher 1938), and the role of this metal ion in insulin secretion and glucose homeostasis was confirmed since then by several reports (Chimienti 2013;Sladek et al 2007). Airways inflammation, one of the main hallmarks of asthma, has also been associated with deregulated zinc homeostasis (Zalewski et al 2005).…”

Section: Introductionmentioning

confidence: 94%

Zinc proteome interaction network as a model to identify nutrient-affected pathways in human pathologies

et al. 2014

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Zinc is an essential micronutrient playing fundamental roles in cellular metabolism. It acts mostly through binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Full annotation of zinc-binding proteins showed them to represent about 10 % of the human proteome, with over 300 enzymes containing zinc ions within their catalytic domains. Also, hundreds of key regulatory proteins, including transcription factors, require zinc for their activity. In this study, the whole set of zinc-binding proteins together with their direct interactors was listed and defined as the zinc proteome (ZNP). We interrogated pathway analysis tools to identify the cellular processes that are predicted to be affected by zinc availability. Network and functional enrichment analyses highlighted biological processes potentially affected by deregulated zinc homeostasis. This computational approach was also tested on a real case study: The possible involvement of ZNP network proteins in Crohn's disease pathogenesis was assessed on genes transcriptionally regulated in the intestine of patients affected by this condition. The analysis produced a network of pathways likely to be influenced by zinc and associated with Crohn's disease. These results highlight a central role for zinc in the tissue remodeling process which occurs upon gut inflammation, pointing at novel disease pathways whose effect could be worsened by zinc dyshomeostasis and impaired zinc fluxes in specific damaged areas. Overall, our computational approach could provide novel insights into pathological conditions and could therefore be used to drive mechanistic research in under-investigated fields of research. An interactive version of the determined ZNP network is available at URL http://93.63.165.11/ZNnetwork/.

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Zinc, pancreatic islet cell function and diabetes: new insights into an old story

Cited by 106 publications

References 114 publications

Advances in the molecular understanding of biological zinc transport

Advances in the molecular understanding of biological zinc transport

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism

Zinc proteome interaction network as a model to identify nutrient-affected pathways in human pathologies

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