GLUT4 repression in response to oxidative stress is associated with reciprocal alterations in C/EBP alpha and delta isoforms in 3T3-L1 adipocytes.

Insulin responsiveness of adipocytes is acquired during normal adipogenesis, and is essential for maintaining whole-body insulin sensitivity. Differentiated adipocytes exposed to oxidative stress become insulin resistant, exhibiting decreased expression of genes like the insulin-responsive glucose transporter GLUT4. Here we assessed the effect of oxidative stress on DNA binding capacity of C/EBP isoforms known to participate in adipocyte differentiation, and determine the relevance for GLUT4 gene regulation.

Proposed mechanisms for the induction of insulin resistance by oxidative stress.

In diabetes (type 1 and type 2), increased flux of free fatty acids and glucose is associated with increased mitochondrial reactive oxygen species (ROS) production and, as a consequence, increased oxidative stress. ROS have been shown to activate various cellular stress-sensitive pathways, which can interfere with cellular signaling pathways. Exposure of different cell lines to micromolar concentrations of hydrogen peroxide leads to the activation of stress kinases such as c-Jun N-terminal kinase, p38, I kappaB kinase, and extracellular receptor kinase 1/2.