Environmental toxicant exposures and type 2 diabetes mellitus: Two interrelated public health problems on the rise

Abstract

Rates of type 2 diabetes mellitus (T2DM) are rising rapidly across the globe and the impact of this devastating disease threatens to plague the 21 century. While some contributing factors are well-recognized (e.g. sedentary lifestyles and caloric excess), others diabetes-promoting risk factors are less established or poorly appreciated. The latter category includes environmental exposures to diabetogenic contaminants. Herein we review some of the latest concepts and mechanisms by which environmental exposures may contribute to rising rates of T2DM with a particular focus on mechanisms involving mitochondrial dysfunction and imbalances in reactive oxygen species (ROS). Furthermore, while the pathogenesis of diabetes includes impairments in insulin sensitivity as well as insulin secretion, we will specifically delve into the links between environmental exposures to toxicants such as arsenic and disruptions in insulin release from pancreatic β-cells. Since β-cell death or dysfunction lies at the heart of both T2DM as well as type 1 diabetes mellitus (T1DM), environmental endocrine disrupting chemicals (EDCs) that disrupt the production or regulated release of the glucose-lowering hormone insulin are likely contributors to diabetes risk. Importantly, understanding the contribution of toxicants to diabetes risk as well as improved understanding of their mechanisms of action offer unique opportunities to modulate diabetes risk via targeted therapeutics or public policy interventions to reduce and remediate exposures.

POHaD: why we should study future fathers

“…Humans are exposed to environmental chemicals on a daily basis, such as EDCs found in personal care products [ 56 ], plastics or food packaging [ 57 ] and the surrounding environment [ 58 ]. EDCs are known to disrupt the endocrine and metabolic homeostasis in the body, but other potential consequences include decreased reproductive function [ 57 , 59 , 60 ], neurodevelopmental delays in children [ 61 ] and increased risk of diabetes [ 62 ], or other chronic disorders via transgenerational inheritance of these exposures [ 63 ]. A worrisome observation is the fact that exposure to EDCs has increased >10-fold over the past ten years [ 64 ].…”

The developmental basis of disease: Update on environmental exposures and animal models

“…It is now clear that type 2 diabetes and non-alcoholic fatty liver disease can also be programmed in utero and early life by exposure to environmental chemicals in animal models. 40,42,43 An examination of environmental chemicals that caused obesity, type 2 diabetes or fatty liver diseases showed that exposure to many of the same chemicals led to all three diseases. Thus, it has been proposed that they should be called metabolism disrupting chemicals (MDCs or metabolism disruptors) as they can lead to metabolic syndrome.…”

Braving the Element: Pancreatic β-Cell Dysfunction and Adaptation in Response to Arsenic Exposure

“…While tremendous stress may be placed on β-cells from a metabolic standpoint, they also face other insults from environmental factors such as endocrine-disrupting chemicals (EDCs). EDCs may work alone or synergistically to derange the normal compensatory mechanisms enabling β-cells to promote glucose tolerance in insulin-resistant individuals (6). In this sense, EDCs may act as drivers of diabetes risk, becoming more deleterious as they compound with lifestyle factors and genetic susceptibilities.…”