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

Aleksandra Buha,Jean-Marc Moulis,Zorica Bulat,Danijela Đukić-Ćosić,Biljana Antonijević,David Wallace,Marina Goumenou,Marijana Ćurčić

doi:10.3390/toxics8030063

Abstract

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.

Highlights

Insulin-mediated glucose disposal widely varies in its sensitivity across populations [1], and depending on the level of compensatory hyperinsulinemia, resistance to insulin can or cannot be overcome
The present review aims to provide an overview of the potential role of Cd exposure in insulin resistance (IR) collected in human, animal, and cell studies, focusing mainly on those conducted in the last two decades
The primary glucose transporter stimulated by insulin is GLUT4, and an early study suggests that Cd exposure decreases the activity of the GLUT1 transporter [89]

Summary

Introduction

Insulin-mediated glucose disposal widely varies in its sensitivity across populations [1], and depending on the level of compensatory hyperinsulinemia, resistance to insulin can or cannot be overcome. Our interest is focused on the actions of cadmium (Cd) and its ability to alter numerous cell and organ systems This toxic metal is characterized by a high soil-to-plant transfer rate, which makes the dietary exposure to this metal inevitable and a matter of great public health concern [14,15]. Wallace et al [37] have summarized the most critical mechanisms of Cd toxicity: changes in gene expression and DNA repair, interference with autophagy and apoptosis pathways, oxidative stress induction, interaction with bioelements, and epigenetic modifications These mechanisms underlie the possible role of Cd as a metabolic disruptor. The present review aims to provide an overview of the potential role of Cd exposure in IR collected in human, animal, and cell studies, focusing mainly on those conducted in the last two decades. The review will briefly discuss the existence of a threshold for this effect

Insulin Resistance and Cadmium

Non-Pancreatic Cells

Pancreatic Cells

Findings

Conclusions and Remarks for Future