Increased FFAs can cause oxidative stress and
activation of JNK pathway. JNK pathway is believed to be strongly associated
with obesity involved in impairment of insulin signalling. Thus, it leads to
insulin resistance in cells and tissue that are dependent on insulin.
Activation of JNK pathway leads to increasing phosphorylation of serine residue
IRS-1 which no longer functions towards to PI3K protein. The inhibition of
PI3K, reduce the expression of Akt protein which inactivate GLUT4 to take up
glucose into the cells. This causes the elevation of glucose in the bloodstream
and hyperinsulinemia outside the cell membrane (Adapted from Shoelson et al., 2006 and Go, Uysal, & Maeda, 2002).
References:
1-Go, C. Z., Uysal, K. T., & Maeda, K. (2002). A central
role for JNK in obesity and insulin resistance, 2, 10–13.
2-Shoelson, S. E., Lee, J., & Goldfine, A. B. (2006).
Review series Inflammation and insulin resistance. The Journal of Clinical
Investigation, 116(7), 1793–1801.
http://doi.org/10.1172/JCI29069.and
