Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Fukunaka, Ayako; Fujitani, Yoshio

doi:10.3390/ijms19020476

Cited by 192 publications

(123 citation statements)

References 84 publications

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“…Obesity has been associated with lower levels of Se, Fe, and Zn in the general population [54,55,[59][60][61], though there are also discrepancies which is consistent with our negative relationship between maternal prepregnancy BMI and Se or Fe [62]. The statistically and positive relationships between Cu levels and prepregnancy BMI found in our study are also confirmed in the literature and is explained by the increase in Cu-binding ceruloplasmin (acute phase protein) [63].…”

Section: Discussionsupporting

confidence: 90%

First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications

Lewandowska

Więckowska

Sajdak³

et al. 2020

Nutrients

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Microelements involved in the oxidative balance have a significant impact on human health, but their role in pregnancy are poorly studied. We examined the relationships between first trimester levels of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu), as well as maternal characteristics and pregnancy results. The data came from a Polish prospective cohort of women in a single pregnancy without chronic diseases. A group of 563 women who had a complete set of data, including serum microelements in the 10–14th week was examined, and the following were found: 47 deliveries <37th week; 48 cases of birth weight <10th and 64 newborns >90th percentile; 13 intrauterine growth restriction (IUGR) cases; 105 gestational hypertension (GH) and 15 preeclampsia (PE) cases; and 110 gestational diabetes mellitus (GDM) cases. The microelements were quantified using mass spectrometry. The average concentrations (and ranges) of the elements were as follows: Se: 60.75 µg/L (40.91–125.54); Zn: 618.50 µg/L (394.04–3238.90); Cu: 1735.91 µg/L (883.61–3956.76); and Fe: 1018.33 µg/L (217.55–2806.24). In the multivariate logistic regression, we found that an increase in Se of 1 µg/L reduces the risk of GH by 6% (AOR = 0.94; p = 0.004), the risk of IUGR by 11% (AOR = 0.89; p = 0.013), and the risk of birth <34th week by 7% (but close to the significance) (AOR = 0.93; p = 0.061). An increase in Fe of 100 µg/L reduces the risk of PE by 27% (AOR = 0.73; p = 0.009). In the multivariable linear regression, we found negative strong associations between prepregnancy BMI, Se (β = −0.130; p = 0.002), and Fe (β = −0.164; p < 0.0001), but positive associations with Cu (β = 0.320; p < 0.000001). The relationships between Se and maternal age (β = 0.167; p < 0.0001), Se and smoking (β = −0.106; p = 0.011) and Cu, and gestational age from the 10–14th week (β = 0.142; p < 0.001) were also found. Secondary education was associated with Zn (β = 0.132; p = 0.004) and higher education was associated with Cu (β = −0.102; p = 0.023). A higher financial status was associated with Fe (β = 0.195; p = 0.005). Other relationships were statistically insignificant. Further research is needed to clarify relationships between first trimester microelements and pregnancy complications. In addition, attention should be paid to lifestyle-related and socioeconomic factors that affect microelement levels.

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Section: Discussionsupporting

confidence: 90%

First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications

Lewandowska

Więckowska

Sajdak³

et al. 2020

Nutrients

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“…On the pancreatic front, there are two common disorders in which MR detection of Zn 2+ secretion may help inform: diabetes mellitus and chronic pancreatitis. It is very well known that Zn 2+ is a crucial factor in the crystallization and storage of insulin [ 78 , 79 ], showing a broader impact of zinc on both types of diabetes [ 12 ]. β-cell function, glucose metabolism, insulin activity, and pathogenesis of diabetes are directly linked to zinc homeostasis [ 12 , 102 , 103 ].…”

Section: Detection Of Zinc With Magnetic Resonance Imagingmentioning

confidence: 99%

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

2020

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Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the most commonly used agents in both the clinical and research environments. Zinc is an essential element involved with over 3000 different cellular proteins, and disturbances in tissue levels of zinc have been linked to a wide range of pathologies, including Alzheimer’s disease, prostate cancer, and diabetes mellitus. MR contrast agents that respond to the presence of Zn2+ in vivo offer the possibility of imaging changes in Zn2+ levels in real-time with the superior spatial resolution offered by MRI. Such responsive agents, often referred to as smart agents, are typically composed of a paramagnetic metal ion with a ligand encapsulating it and one or more chelating units that selectively bind with the analyte of interest. Translation of these agents into clinical radiology is the next goal. In this review, we discuss Gd3+-based MR contrast agents that respond to a change in local Zn2+ concentration.

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“…Studies by others and our group suggest that AβPs directly incorporate into the membrane and form channels (pores) that allow the passage of Ca 2+ and other cations, and that the resulting change in [Ca 2+ ] i may be a primary pathogenetic event in AβP neurotoxicity [110][111][112]. Neurotoxic peptide fragments of AβP, including AβP(1-40), AβP (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and AβP , have been demonstrated to incorporate into artificial planar lipid membranes and form giant multi-level pores (~5 nS) with cation (including Ca 2+ ) selectivity [113][114][115]. To assess the validity of this amyloid channel hypothesis, we performed an electrophysiological study to examine whether AβPs form channels on neuronal cell membranes as well as on liposomes.…”

Section: Aβp-induced Ca Dyshomeostasismentioning

confidence: 98%

“…ZIP transporters control Zn 2+ influx into cells or subcellular organs such as the Golgi apparatus or endoplasmic reticulum (ER). Disorders of Zn 2+ transporters have been shown to cause Ehlers-Danlos syndrome and other human diseases [25]. Metallothioneins (MTs), such as MT1, MT2, and MT3, also regulate Zn 2+ homeostasis [26].…”

Section: Neurometals In the Brainmentioning

confidence: 99%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

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Conformational changes in amyloidogenic proteins, such as β-amyloid protein, prion proteins, and α-synuclein, play a critical role in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease, prion disease, and Lewy body disease. The disease-associated proteins possess several common characteristics, including the ability to form amyloid oligomers with β-pleated sheet structure, as well as cytotoxicity, although they differ in amino acid sequence. Interestingly, these amyloidogenic proteins all possess the ability to bind trace metals, can regulate metal homeostasis, and are co-localized at the synapse, where metals are abundantly present. In this review, we discuss the physiological roles of these amyloidogenic proteins in metal homeostasis, and we propose hypothetical models of their pathogenetic role in the neurodegenerative process as the loss of normal metal regulatory functions of amyloidogenic proteins. Notably, these amyloidogenic proteins have the capacity to form Ca2+-permeable pores in membranes, suggestive of a toxic gain of function. Therefore, we focus on their potential role in the disruption of Ca2+ homeostasis in amyloid-associated neurodegenerative diseases.

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Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Cited by 192 publications

References 84 publications

First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications

First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Amyloids: Regulators of Metal Homeostasis in the Synapse

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