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Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

ABSTRACT: A widely prevalent single nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is associated with an increased risk for T2DM. ZnT8 is mostly expressed in pancreatic insulin-producing islets of Langerhans. The effect of this variant on the divalent metal profile in human islets is unknown. Additionally, essential and non-essential divalent metal content of human islets under normal environmental exposure conditions has not been described. We therefore examined the correlation of zinc and other divalent metals in human islets with rs13266634 genotype and demographic characteristics. We found that the diabetes risk genotype C/C at rs13266634 is associated with higher islet Zn concentration (C/C genotype: 16792?±?1607, n?=?22, C/T genotype: 11221?±?1245, n?=?18 T/T genotype: 11543?±?6054, n?=?3, all values expressed as mean nmol/g protein?±?standard error of the mean, p?=?0.040 by ANOVA). A positive correlation between islet cadmium content and both age (p?=?0.048, R2?=?0.09) and female gender (women: 36.88?±?4.11?vs men: 21.22?±?3.65?nmol/g protein, p?=?0.007) was observed. Our results suggest that the T2DM risk allele C is associated with higher islet zinc levels and support prior evidence of cadmium's higher bioavailability in women and its long tissue half-life.

SUBMITTER: Wong WP

PROVIDER: S-EPMC5428289 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

Wong Winifred P WP Allen Norrina B NB Meyers Matthew S MS Link Emma O EO Zhang Xiaomin X MacRenaris Keith W KW El Muayed Malek M

Scientific reports 20170328 1

A widely prevalent single nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is associated with an increased risk for T2DM. ZnT8 is mostly expressed in pancreatic insulin-producing islets of Langerhans. The effect of this variant on the divalent metal profile in human islets is unknown. Additionally, essential and non-essential divalent metal content of human islets under normal environmental exposure conditions has not been described. We therefore examin ...[more]

PMID: 28352089

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Project description:We describe 2 artificial stream experiments that exposed aquatic insect communities to zinc (Zn), copper (Cu), and cadmium (year 2014) and to Zn, Cu, and nickel (year 2015). The testing strategy was to concurrently expose insect communities to single metals and mixtures. Single-metal tests were repeated to evaluate the reproducibility of the methods and year-to-year variability. Metals were strongly accumulated in sediments, periphyton, and insect (caddisfly) tissues, with the highest concentrations occurring in periphyton. Sensitive mayflies declined in metal treatments, and effect concentrations could be predicted effectively from metal concentrations in either periphyton or water. Most responses were similar in the replicated tests, but median effect concentration values for the mayfly Rhithrogena sp. varied 20-fold between the tests, emphasizing the difficulty comparing sensitivities across studies and the value of repeated testing. Relative to the single-metal responses, the toxicity of the mixtures was either approximately additive or less than additive when calculated as the product of individual responses (response addition). However, even less-than-additive relative responses were sometimes greater than responses to similar concentrations tested singly. The ternary mixtures resulted in mayfly declines at concentrations that caused no declines in the concurrent single-metal tests. When updating species-sensitivity distributions (SSDs) with these results, the mayfly responses were among the most sensitive 10th percentile of available data for all 4 metals, refuting older literature placing mayflies in the insensitive portion of metal SSDs. Testing translocated aquatic insect communities in 30-d artificial streams is an efficient approach to generate multiple species effect values under quasi-natural conditions that are relevant to natural streams. Environ Toxicol Chem 2020;39:812-833. Published 2020 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America.

Dataset Information

Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

Publications

Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

Similar Datasets

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