Arsenic is more potent than cadmium or manganese in disrupting the INS-1 beta cell microRNA landscape

Beck, Rowan; Chandi, Mohit; Kanke, Matt; Stýblo, Miroslav; Sethupathy, Praveen

doi:10.1007/s00204-019-02574-8

Cited by 20 publications

(16 citation statements)

References 68 publications

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“…Synthetic delivery of manganese can also suppress lipid peroxidation in kidneys and downregulate the expression of genes known to promote diabetic complications such as nephropathy (Khan et al 2009). Although supplementation can lower oxidative stress in multiple tissue sites, manganese can also increase pancreatic islet amyloid formation, which can inhibit glucose-simulated insulin secretion in vitro (Mirhashemi & Shahabaddin 2011, Beck et al 2019. Overall, there is evidence that manganese can promote antioxidant responses that lower blood glucose, but correlations of blood or urinary levels of manganese to blood glucose levels should consider retention and excretion of this micronutrient.…”

Section: Manganesementioning

confidence: 99%

Micronutrients impact the gut microbiota and blood glucose

Barra

Anhê

Cavallari

et al. 2021

Journal of Endocrinology

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Micronutrients influence hormone action and host metabolism. Dietary minerals, trace elements and vitamins can alter blood glucose and cellular glucose metabolism and several micronutrients are associated with risk and progression of type 2 diabetes. Dietary components, microbes and host immune, endocrine, and metabolic responses all interact in the intestine. There has been a focus on macronutrients modifying the host-microbe relationship in metabolic disease. Micronutrients are positioned to alter host-microbe symbiosis that participates in host endocrine control of glucose metabolism. Minerals and trace elements can alter the composition of the intestinal microbiota, gut barrier function, compartmentalized metabolic inflammation, cellular glucose transport and endocrine control of glucose metabolism, including insulin and thyroid hormones. Dietary vitamins also influence the composition of the intestinal microbiota and vitamins can be biotransformed by gut microbes. Host-microbe regulation of vitamins can alter immunity, lipid and glucose metabolism, and cell fate and function of pancreatic beta cells. Causal effects of micronutrients in host-microbe metabolism are still emerging and the mechanisms linking dietary excess or deficiency of specific micronutrients to changes in gut microbes directly linked to metabolic disease risk are not yet clear. Dietary fiber, fat, protein, and carbohydrates are key dietary factors that impact how microbes participate in host glucose metabolism. It is possible that micronutrient and microbiota-derived factors also participate in host-microbe responses that tip the balance in endocrine control of host glucose metabolism. Dietary micronutrients should be considered, tested, and controlled in preclinical and clinical studies investigating host-microbe factors in metabolic diseases.

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Section: Manganesementioning

confidence: 99%

Micronutrients impact the gut microbiota and blood glucose

Barra

Anhê

Cavallari

et al. 2021

Journal of Endocrinology

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“…Examination of β-cell function after arsenic, manganese, and Cd exposure revealed a distinct pattern of miRNA expression changes unique to each element, suggesting that biochemical differences result in distinct responses. Exposure to inorganic arsenic gave rise to a significant 76% increase in miR-146a, while there was a 60% decrease in miR-195 expression following Cd exposure [95]. Since β-cells are excitable cells and involve cell depolarization, leading to insulin release, several studies have examined the effects of metal exposure on voltage-gated calcium channel function.…”

Section: Pancreatic Cellsmentioning

confidence: 99%

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Buha

Đukić-Ćosić

Ćurčić

et al. 2020

Toxics

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Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

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“…We have previously shown that trivalent arsenicals, arsenite (iAs III ) and its methylated metabolite MAs III , significantly impair GSIS in INS1 832/13 cells (Beck et al 2019 ; Dover et al 2018 ) and isolated murine islets (Douillet et al 2013 ; Huang et al 2019 ). In this study, we first sought to confirm that exposure to arsenicals leads to reduced GSIS in INS1 832/13 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As previously described (Beck et al 2019 ), INS-1 832/13 cells were seeded at 1,000,000 cells/well in a 12-well plate 24 h prior to beginning experiments. Cells were then exposed to either iAs III or MAs III for 24 h. After 24 h cells cell culture media was replaced with secretion assay buffer (SAB), which consists of 114 mM NaCl, 4.7 MM KCl, 1.2 mM KH 2 PO 4 , 1.16 mM MgSO 4 , 20 mM HEPES, 2.5 mM CaCl 2 , 0.2% bovine serum albumin, 25.5 mM NaHCO 3 , and 0 mM of glucose.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies by our group and others have shown that trivalent arsenicals impair GSIS in both isolated murine islets as well as rodent beta cell lines (Douillet et al 2013 ; Huang et al 2019 ; Díaz-Villaseñor et al 2006 ). More recently, we have demonstrated that iAs III alters the microRNA (miRNA) landscape in beta cells much more substantially than other metals that can also affect GSIS, suggesting that miRNAs may play an important role in the mechanisms underlying the inhibition of GSIS by iAs III (Beck et al 2019 ; Beck et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Candidate master microRNA regulator of arsenic-induced pancreatic beta cell impairment revealed by multi-omics analysis

et al. 2022

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Arsenic is a pervasive environmental toxin that is listed as the top priority for investigation by the Agency for Toxic Substance and Disease Registry. While chronic exposure to arsenic is associated with type 2 diabetes (T2D), the underlying mechanisms are largely unknown. We have recently demonstrated that arsenic treatment of INS-1 832/13 pancreatic beta cells impairs glucose-stimulated insulin secretion (GSIS), a T2D hallmark. We have also shown that arsenic alters the microRNA profile of beta cells. MicroRNAs have a well-established post-transcriptional regulatory role in both normal beta cell function and T2D pathogenesis. We hypothesized that there are microRNA master regulators that shape beta cell gene expression in pathways pertinent to GSIS after exposure to arsenicals. To test this hypothesis, we first treated INS-1 832/13 beta cells with either inorganic arsenic (iAsIII) or monomethylarsenite (MAsIII) and confirmed GSIS impairment. We then performed multi-omic analysis using chromatin run-on sequencing, RNA-sequencing, and small RNA-sequencing to define profiles of transcription, gene expression, and microRNAs, respectively. Integrating across these data sets, we first showed that genes downregulated by iAsIII treatment are enriched in insulin secretion and T2D pathways, whereas genes downregulated by MAsIII treatment are enriched in cell cycle and critical beta cell maintenance factors. We also defined the genes that are subject primarily to post-transcriptional control in response to arsenicals and demonstrated that miR-29a is the top candidate master regulator of these genes. Our results highlight the importance of microRNAs in arsenical-induced beta cell dysfunction and reveal both shared and unique mechanisms between iAsIII and MAsIII.

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Arsenic is more potent than cadmium or manganese in disrupting the INS-1 beta cell microRNA landscape

Cited by 20 publications

References 68 publications

Micronutrients impact the gut microbiota and blood glucose

Micronutrients impact the gut microbiota and blood glucose

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Candidate master microRNA regulator of arsenic-induced pancreatic beta cell impairment revealed by multi-omics analysis

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