Table 1.

Example endocrine disruptors and implications in diabetes pathogenesis.

EDC	Insulin secretion	Insulin action	References
Arsenic	• Impaired glucose sensing • Beta cell mitochondrial dysfunction and oxidative stress	• Increased HOMA-IR and reduced skeletal muscle mass • Adipocyte, hepatic, and skeletal inflammation • Impairment of insulin signaling	Zhang et al. (2020) Mondal et al. (2020) Jia et al. (2020); S. Wei et al. (2020) Dover, Patel, and Styblo (2018)
Air pollution		• Increased HOMA-IR • Inflammation and increased expression of inflammatory markers in adipose	Li et al. (2021) Lin et al. (2020) Kim and Lee (2014)
Bisphenol A	• Reduced GIIS and downregulation of insulin related genes • Mitochondrial dysfunction and apoptosis of beta cells	• Increased HOMA-IR • Hepatic DNA methylation and reduction of hepatic glucokinase and overall glucose sensing	Wang et al. (2012) Cimmino et al. (2020) Wei, Ding, Wang, Liu, and Lin (2017) Ma et al. (2013)
DDT/DDE	• Altered beta cell protein expression and toxicity • Impaired GIIS • Reduced insulin mRNA, proinsulin, an insulin content	• Oxidative stress with reduced insulin signaling in skeletal muscle • Adipocyte inflammation	Pavlikova, Sramek, Jelinek, Halada, and Kovar (2020) Singh, Sarkar, Saxena, and Koner (2019) Park, Kim, and Rhyu (2020) Pavlikova, Smetana, Halada, and Kovar (2015) Mangum et al. (2016)
Polychlorinated biphenyls	• Increased insulin release and reduced cellular insulin • Pancreatic atrophy, steatosis, and fibrosis	• Increased adipocyte droplet size and reduced insulin response • Adipocyte inflammation	Fischer, Zhou, and Wagner (1996) Shi et al. (2019) Kim et al. (2017) Baker et al. (2015)
Per/polyfluoroalkyl compounds		• Increased HOMA-IR • Activation of PPAR-α and hepatic steatosis	Cardenas et al. (2017) Shipley et al. (2004) Lv et al. (2013)
Organophosphates	• Pancreatitis and pancreatic necrosis • Oxidative stress • Mitochondrial dysfunction	• Reduced expression of glucose transporters and insulin induced proteins	Farkhondeh et al. (2020) Leonel Javeres et al. (2020) Karami-Mohajeri and Abdollahi (2013), Nurulain, Szegi, Tekes, and Naqvi (2013) Hou et al. (2019) Wang et al. (2018)
Polycyclic aromatic hydrocarbons (PAHs)	• β-cell oxidative stress and toxicity	• Suppression of insulin signaling pathway • Inhibition of beta-adrenergic receptors • Oxidative stress	Fang et al. (2020) Irigaray et al. (2006), Smiljevska-Ristovska et al. (2020) Hu, Kan, Kearney, and Xu (2015)
Neonicotinoid insecticides	• DNA damage • Glutathione reduction	• Increased weight gain, adiposity, and insulin resistance thorough inhibition of downstream signaling molecules and phosphorylation	Kara, Ozta, and Ozhan (2020) Sun et al. (2017)
Phthalates	• Reduced β-cell mass and insulin content • Altered expression of genes involved insulin production and pancreatic development • Induce apoptosis	• Epigenetic modifications in skeletal muscle with increased oxidative stress	Lin et al. (2011) Li et al. (2021) Wei et al. (2020)
Heavy metals (cadmium, mercury, etc.)	• Cytotoxicity due to decreased ATP • Inhibit GIIS • Mitochondrial swelling and permeation of membranes • Oxidative stress	• Increased HOMA-IR • Mitochondrial dysfunction	Elmorsy, Al-Ghafari, Al Doghaither, and Ghulam (2021) Buha et al. (2020) Wang et al. (2020) Dover et al. (2018) Kim and Lee (2014)
2,3,7,8-Tetrachlorodibenzodioxin	• Disruption in calcium signaling	• Inflammatory cytokine activation	Ruiz, Perlina, Mumtaz, and Fowler (2016) Rasinger, Carroll, Lundebye, and Hogstrand (2014)
Vacor	• Inhibition of mitochondrial oxidative phosphorylation • Islet necrosis and inflammation		Miller, Stokes, and Silpipat (1978), Taniguchi et al. (1989)
Triphenyltin	• Induces β-cell apoptosis • Reduced ATP production • Reduced calcium signaling	• Reduced insulin signaling in adipose, skeletal, and hepatic tissue	Li et al. (2017), Miura et al. (2012), Zuo et al. (2014)
Alloxan	• Inhibits glucose sensing, glucokinase, and GIIS • Oxidative stress • β-cell necrosis	• Inhibition of insulin signaling	Lenzen (2008) Ader, Richey, and Bergman (1998)