Decreased function of these GLUT4-interacting proteins may impair mitochondrial metabolism, thus altering the ability to switch between carbohydrates and fats as a source of oxidative energy. Furthermore, changes in the function of GLUT4-interacting proteins may alter how sensors of energy stress signal imbalance. One such sensor, AMP-activated protein kinase, signals via the transcriptional coactivator of peroxisome proliferator activated receptor, PGC-1a. The latter induces mitochondrial biogenesis and increases the concentration of GLUT4 in the muscle. However, F can cause changes in the expression of mitochondrial proteins, leading to functional Jatropholone-B alterations in mitochondria, and altered mitochondrial function can lead to oxidative stress. In the present study, stress-related proteins and anti-oxidant markers that interact with GLUT4 were down-regulated in D animals exposed to 10 ppm F. Downregulation of proteins, such as heat shock protein HSPB8 and GRP78, indicates a 4SC-202 reduced tolerance to stress in D rats exposed to F. Oxidative stress also decreases the gene and protein expression levels of GLUT4. Decreased GLUT4 expression might be expected to result in a decrease of the glucose uptake, thus leading to IR. When insulin-resistant mice are exposed to aerobic exercise, the expression of heat shock proteins increases. Therefore, exercise may play a key role in improving IR. Similarly, when exposed to F, D animals display an increase in oxidative stress due to the concomitant reduction of mitochondrial proteins, such as MDH and the stress proteins HSPB8 and GRP78. The reduction of these two latter proteins indicates an increase in IR, which might exacerbate diabetes. When the concentration of F is increased to 50 ppm, the stress proteins were not altered in D animals. Absence of a dosedependent response was also reported in a study, where treatment of rats with 25 ppm F led to histological alterations in liver, while treatments with 5 or 50 ppm F did not. This observation may be due to the organism adapting to a dose of F that, in the short term, might lead to high levels of toxicity but diminishes in toxicity over the long term.