Abstract
Cadmium (Cd) is an environmental endocrine disruptor. Despite increasing research about the metabolic effects of Cd on HepG2 cells, information about the metabolic effects of Cd on insulin resistance HepG2 (IR-HepG2) cells is limited. Currently, most individuals with diabetes are exposed to Cd due to pollution. Previously, we reported that Cd exposure resulted in decreased blood glucose levels in diabetic mice, the underlying mechanism deserves further study. Therefore, we used palmitic acid (0.25 mM) to treat HepG2 cells to establish IR-HepG2 model. IR-HepG2 cells were exposed to CdCl2 (1 μM and 2 μM). Commercial kits were used to measure glucose production, glucose consumption, ROS and mitochondrial membrane potential. Western blot and qRT-PCR were used to measure the proteins and genes of glucose metabolism. In the current study setting, we found no significant changes in glucose metabolism in Cd-exposed HepG2 cells, but Cd enhanced glucose uptake, inhibited gluconeogenesis and activated the insulin signaling pathway in IR-HepG2 cells. Meanwhile, we observed that Cd caused oxidative stress and increased the intracellular calcium concentration and inhibited mitochondrial membrane potential in IR-HepG2 cells. Cd compensatingly increased glycolysis in IR-HepG2 cells. Collectively, we found Cd ameliorated glucose metabolism disorders in IR-HepG2 cells. Furthermore, Cd exacerbated mitochondrial damage and compensatory increased glycolysis in IR-HepG2 cells. These findings will provide novel insights for Cd exposure in insulin resistant individuals.