Evaluating combined effects of chronic, low-dose exposures of cadmium (CLEC) and hyperglycemia on insulin signaling dysfunction in a hepatocellular model.

ABSTRACT: The pathophysiological effects of chronic heavy metal exposures on human health remains uncertain. In this study, we developed a novel chronic, low-dose exposure of Cadmium (CLEC) model using the hepatocellular cell lines, HepG2 and HUH7. We modulated cell culture conditions to mimic human normoglycemic (5.6 mM) and hyperglycemic (15 mM) states with concomitant cadmium (Cd) exposures for 24 weeks. CLEC cells undergo non-trivial alterations in glucose signaling and metabolic characteristics within our model. We observe elevated baseline reactive oxygen species (ROS) production and decreased 2-NBDG uptake indicative of glucose metabolic dysfunction. Additionally, induction of metallothionein (MT) expression, increased activation of Akt signaling (via phosphorylation) and reduced IRS-2 protei

SUBMITTER: Kumar R 

PROVIDER: S-EPMC11573001 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature