Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Sci Rep. 2017 Mar 28;7(1):473. doi: 10.1038/s41598-017-00394-3.
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, R = 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.
一个普遍存在的单核苷酸多态性，即 SLC30A8 基因编码的锌转运蛋白 ZnT8 中的 rs13266634，与 T2DM 的风险增加有关。ZnT8 主要在胰岛的胰岛细胞中表达。这种变体对人胰岛中二价金属谱的影响尚不清楚。此外，在正常环境暴露条件下，人胰岛中二价金属的必需和非必需含量尚未描述。因此，我们研究了锌和人胰岛中二价金属与 rs13266634 基因型和人口统计学特征的相关性。我们发现，rs13266634 上的糖尿病风险基因型 C/C 与胰岛 Zn 浓度较高相关（C/C 基因型：16792±1607，n=22，C/T 基因型：11221±1245，n=18，T/T 基因型：11543±6054，n=3，所有值均表示为平均 nmol/g 蛋白±均数的标准误差，ANOVA 分析 p=0.040）。胰岛镉含量与年龄呈正相关（p=0.048，R=0.09），与性别呈正相关（女性：36.88±4.11 vs 男性：21.22±3.65 nmol/g 蛋白，p=0.007）。我们的结果表明，T2DM 风险等位基因 C 与胰岛锌水平升高有关，并支持镉在女性中生物利用度较高及其长组织半衰期的先前证据。
