The Hijacking of Cellular Signaling and the Diabetes Epidemic: Mechanisms of Environmental Disruption of Insulin Action and Glucose Homeostasis

Abstract

The burgeoning epidemic of metabolic disease causes significant societal and individual morbidity and threatens the stability of health care systems around the globe. Efforts to understand the factors that contribute to metabolic derangements are critical for reversing these troubling trends. While excess caloric consumption and physical inactivity superimposed on a susceptible genetic background are central drivers of this crisis, these factors alone fail to fully account for the magnitude and rapidity with which metabolic diseases have increased in prevalence worldwide. Recent epidemiological evidence implicates endocrine disrupting chemicals in the pathogenesis of metabolic diseases. These compounds represent a diverse array of chemicals to which humans are exposed via multiple routes in adulthood and during development. Furthermore, a growing ensemble of animal- and cell-based studies provides preclinical evidence supporting the hypothesis that environmental contaminants contribute to the development of metabolic diseases, including diabetes. Herein are reviewed studies linking specific endocrine disruptors to impairments in glucose homeostasis as well as tying these compounds to disturbances in insulin secretion and impairments in insulin signal transduction. While the data remains somewhat incomplete, the current body of evidence supports the hypothesis that our chemically polluted environment may play a contributing role in the current metabolic crisis.

Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE

“…Supporting these warnings are, among others, several epidemiological and in vivo studies that reported the positive correlation of EDCs concentrations, both in AT and plasma, with the prevalence of obesity, MetS, insulin resistance, hypertension and CVD 21–23 , as well as adipocyte dysfunction 24 .…”

Fatores De Risco Para Ulceração No Pé De Indivíduos Com Diabetes Mellitus Tipo 2

“…Sua complexidade associada à elevada incidência e prevalência concorrem para que essa doença seja considerada um importante problema de saúde pública (2) .…”

“…O pé diabético ocorre quando uma área lesionada ou infeccionada nos pés desenvolve úlcera (5) . Acomete cerca de 15% dos pacientes com DM ao longo da vida e é responsável por mais de 60% das amputações não traumáticas (1)(2) , o que consequentemente gera ampla repercussão social e econômica (6) .…”

More β-cell researchers are wanted!

“…Another potentially productive research area in b-cell failure is the various interactions of b-cell function with environmental factors (e.g., endocrine disruptors such as arsenic), as well as genetic and epigenetic factors. This is especially relevant to the task of solving the evolving diabetes epidemic in developing countries [6]. Due to the development of new techniques and our understanding of b-cell biology, the research areas included in these three themes represent numerous and increasing opportunities for investigators, both established and new, to develop novel diabetes therapies.…”