Cadmium exposure impairs pancreatic β-cell function and exaggerates diabetes by disrupting lipid metabolism. (April 2021)

• Record Type: Journal Article
• Authors: Hong, Huihui; Xu, Yudong; Xu, Jia; Zhang, Jingjing; Xi, Yu; Pi, Huifeng; Yang, Lingling; Yu, Zhengping; Wu, Qingqian; Meng, Zhuoxian; Ruan, Wei-Shuyi; Ren, Yunzhao; Xu, Shuzhen; Lu, Yuan-Qiang; Zhou, Zhou
• Is Part Of: Environment international. Volume 149(2021)
• Publication Date: 2021-04
• Subjects: Cadmium -- Pancreatic β-cells -- Diabetes -- Lipid metabolism -- Inflammation; AcCa Acyl carnitine -- ATGL Adipose triglyceride lipase -- Cer Ceramides -- CerG1/CerG2 Simple Glc series -- Cd Cadmium -- ChE Cholesterol ester -- Co Coenzyme -- DG Diglyceride -- FA Fatty acid -- GM3 Gangliosides -- GSIS Glucose-stimulated insulin secretion -- HDL-C High-density lipoproteincholesterol -- H&E Hematoxylin-Eosin -- HSL Hormone-sensitive lipase -- IpGTT Intraperitoneal glucose tolerance test -- LCFA Long chain fatty acid -- LD Lipid droplet -- LDL-C Low-density lipoproteincholesterol -- LPC Lysophosphatidylcholine -- LPE Lysophosphatidylethanolamine -- LPG Lysophosphatidylglycerol -- LPI Lysophosphatidylinositol -- LPS Lysophosphatidylserine -- MGDG Monogalactosyldiacylglycerol -- MTBE Methyl tert-butyl ether -- OAHFA (O-acyl)-1-hydroxy fatty acid -- OPLS-DA Orthogonal partial least-squares-discriminant analysis -- PC Phosphatidylcholine -- PCA Principal component analysis -- PE Phosphatidylethanolamine -- PFA Paraformaldehyde -- PG Phosphatidylglycerol -- PI/PIP Phosphatidylinositol -- PLS-DA Partial least-squares-discriminant analysis -- PS Phosphatidylserine -- RF Radiofrequency -- RSD Relative standard deviation -- RT Retention time -- SM Sphingomyelin -- So Sphingosine -- SQDG Sulfoquinovosyldiacylglycerol -- SQMG Sulfoquinovosylmonoacylglycerol -- STZ Streptozotocin -- S1P Sphongosine1-phosphate -- TG Triglyceride -- TC Total Cholesterol -- UHPLC-HRMS Ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry -- VLCFA Very long chain fatty acid -- VIP Variable Importance for the Projection; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2021.106406
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Cd exposure induces pancreatic β-cell dysfunction and promotes the development of diabetes. Cd exposure disrupts lipid metabolism and induces lipid accumulation in MIN6 cells. Cd exposure promotes inflammation by increasing the weight of inflammatory bioactive lipids. Abstract: Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to elucidating the mechanisms underlying Cd-induced pancreatic β-cell dysfunction and the role of Cd toxicity in the development of diabetes. In this study, we demonstrated that exposure to Cd caused remarkable pancreatic β-cell dysfunction and death, both in vitro and in vivo . Lipidomic analysis of Cd-exposed pancreatic β-cells using high-resolution mass spectrometry revealed that Cd exposure altered the profile and abundance of lipids. Cd exposure induced intracellular lipid accumulation, promoted lipid biogenesis, elevated pro-inflammatory lipid contents and inhibited lipid degradation. Furthermore, Cd exposure upregulated the expression levels of TNF-α, IL-1β and IL-6 in pancreatic β-cells and elevated the TNF-α, IL1-β and IL-6 levels in the serum and pancreas. Taken together, the results of our study demonstrated that environmental relevant Cd exposure causes pro-inflammatory lipids elevation and insulin secretion dysfunction in β-cells and hence exaggerates diabetes development. Combined exposure to environmental hazardous chemicals might markedly increase the probability of developing diabetes in humans. This study provides new metabolic and pharmacological targets for antagonizing Cd toxicity.