Zinc, zinc transporters and diabetes

Rungby, Jørgen

doi:10.1007/s00125-010-1793-x

Cited by 86 publications

(67 citation statements)

References 33 publications

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“…3 G and H and Movie S4). ZnT8 is highly expressed on the granular membrane of islet β cells (24), and ZnT8 KO mice showed defects in cellular Zn 2+ transport, insulin crystallization, and the formation of dense core granules, suggesting that ZnT8 represents a key Zn 2+ transporter responsible for accumulating the ion in insulin granules (25). Consistent with these studies, the drastically reduced ZIMIR fluorescence in response to stimuli observed in the ZnT8 KO β cells likely reflected a much decreased level of granular Zn 2+ content in these cells.…”

Section: Tration ([Znmentioning

confidence: 99%

Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR)

Chen

Bellomo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

141

174

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Current methods of monitoring insulin secretion lack the required spatial and temporal resolution to adequately map the dynamics of exocytosis of native insulin granules in intact cell populations in three dimensions. Exploiting the fact that insulin granules contain a high level of Zn 2+ , and that Zn 2+ is coreleased with insulin during secretion, we have developed a fluorescent, cell surface-targeted zinc indicator for monitoring induced exocytotic release (ZIMIR). ZIMIR displayed a robust fluorescence enhancement on Zn 2+ chelation and bound Zn 2+ with high selectivity against Ca 2+ and Mg 2+ . When added to cultured β cells or intact pancreatic islets at low micromolar concentrations, ZIMIR labeled cells rapidly, noninvasively, and stably, and it reliably reported changes in Zn 2+ concentration near the sites of granule fusion with high sensitivity that correlated well with membrane capacitance measurement. Fluorescence imaging of ZIMIR-labeled β cells followed the dynamics of exocytotic activity at subcellular resolution, even when using simple epifluorescence microscopy, and located the chief sites of insulin release to intercellular junctions. Moreover, ZIMIR imaging of intact rat islets revealed that Zn 2+ /insulin release occurred largely in small groups of adjacent β cells, with each forming a "secretory unit." Concurrent imaging of ZIMIR and Fura-2 showed that the amplitude of cytosolic Ca 2+ elevation did not necessarily correlate with insulin secretion activity, suggesting that events downstream of Ca 2+ signaling underlie the cell-cell heterogeneity in insulin release. In addition to studying stimulation-secretion coupling in cells with Zn 2+ -containing granules, ZIMIR may find applications in β-cell engineering and screening for molecules regulating insulin secretion on high-throughput platforms.probe development | zinc imaging | hormone secretion assay

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Section: Tration ([Znmentioning

confidence: 99%

Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR)

Chen

Bellomo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

141

174

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“…Since Zn inhibited glycogen synthase kinase 3; Zn deficiency may be related to diabetes as a result of increased excretion resulting from polyuria. Moreover, Zn deficiency impairs insulin release as it is an essential cofactor for insulin synthesis and release [21] [22] [23].…”

Section: Discussionmentioning

confidence: 99%

Variations of Hair Trace Element Contents in Diabetic Females

Saleh¹,

Fatani²,

Adly³

et al. 2017

JBM

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Background: Alterations of trace elements, could induce metabolic disorders as they forthwith participating in the metabolic pathways and play different roles modulating it as well as many enzymes require trace elements for their activation and functions. Of these elements, selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) have been recognized as essentials for metabolism. Hyperglycemia and diabetes mellitus are important causes of mortality and morbidity worldwide, and their global prevalence are growing from 2.8% in 2000 projecting to be 4.4% in 2030. Diabetes is prevalent in Saudi Arabia with high incidence in urbanized areas and its prevalence is estimated to expand 3 times by 2030. Patients and Methods: In total, 75 diabetic women and 80 aberrantly healthy women were recruited. Clinical and familial history was recorded. Hair Se, Zn, Cu and Mn levels were analyzed as well as fasting blood sugar (FBS), glycated hemoglobin (HbA1c). Results: Our findings revealed a marked decrease of Zn and Mn levels in diabetic women hair compared to control group (p < 0.05, p <0.005 respectively). Otherwise, Se and Cu levels were significantly elevated in hair of diabetic patients (p < 0.005, p <0.05 respectively). Conclusion: Diabetes may disrupt the trace elements balance as well as their alterations can affect glucose metabolism and insulin action. Chronic hyperglycemia can cause disturbance of some trace elements which, in turn, can modulate glucose homeostasis. The metabolic dysregulation occurring in hyperglycemia may influence trace element status by increasing excretion, diminishing availability or redistribution of trace elements among different body pools. Hair trace elements can be useful long-term markers for metabolic disturbance; however, larger prospective studies are required to validate their role in diagnosis and follow up applications.

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“…7 Since, the role of Zinc in insulin synthesis and secretion has been established over the years, [18][19][20][21] it is possible that hypozincaemia caused by chronic Frusemide administration may lead to hyperglycemia in normal individuals and deteriorate the condition further in diabetics.…”

Section: Discussionmentioning

confidence: 99%

Effect of Frusemide on Serum and Urinary Zinc levels in Rabbits

Bhat¹,

Khan²

2015

JYP

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Introduction:Zinc is an essential trace element playing a vital role in the maintenance of health. Frusemide, a loop diuretic, is known to deplete sodium, potassium, magnesium and calcium levels. But, very few reports exist on its effect on Zinc levels. Hence, this study was performed on rabbits to investigate the same in detail. Material & Methods: Healthy adult New Zealand White rabbits (n=6 per group) were treated with Normal saline (2 ml kg -1 ) and Frusemide (5, 10 or 15 mg kg -1 each) intraperitoneally. Their serum and urinary zinc levels were studied by Atomic Absorption Spectrophotometry. Analysis of serum Zinc levels was also done after dietary Zinc supplementation for 20 days. Results: A dose-dependent decrease in serum Zinc levels owing to increased urinary Zinc excretion was observed. Both the urinary volume and urinary Zinc concentration increased dose-dependently. The percent fall in serum Zinc occurred in proportion to the pre-treatment serum values. Administration of Zinc in the diet restored the serum Zinc levels to normal. Conclusion: Frusemide may be responsible for Zinc depletion. Supplementation of Zinc may help to prevent the same in patients on prolonged Frusemide therapy.

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Zinc, zinc transporters and diabetes

Cited by 86 publications

References 33 publications

Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR)

Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR)

Variations of Hair Trace Element Contents in Diabetic Females

Effect of Frusemide on Serum and Urinary Zinc levels in Rabbits

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