When blood sugar concentrations are elevated, humans run the risk of glucose binding to proteins in the blood and causing the irreversible formation of advanced glycation end products (AGE). Once formed, AGEs can bind to their receptor (RAGE) and stimulate inflammation and oxidative stress. This pathological signaling can be stopped by pieces of the RAGE protein that break off and form a soluble version called sRAGE. These soluble versions of RAGE are good because they can bind excess AGEs and prevent their effects.
A new study published in the American Journal of Physiology - Endocrinology and Metabolism measured sRAGE levels in overweight and obese individuals to determine if changes in sRAGE could help explain how diabetes develops. What they found was that levels of sRAGE were significantly lower in people with obesity, insulin resistance or type 2 diabetes. Less sRAGE in these individuals means more AGEs in the circulation that can cause harm. The hope is to use this information to help develop new ways to prevent or treat diabetes.
What is interesting about the RAGE protein is that it did not show up on the evolutionary tree until mammals arrived (see prior post). So, animals like birds, which are known to have very high blood sugar, do not express this protein. So how might they protect their tissues from glucose interactions with proteins? The answer appears to lie within the proteins themselves. In fact, another recent study published in Comparative Biochemistry and Physiology shows that although circulating glucose concentrations are high, glycation of albumin is low in comparison to humans.
Miranda ER, Somal VS, Mey JT, Blackburn BK, Wang E, Farabi S, Karstoft K, Fealy CE. Kashyap S, Kirwan JP, Quinn L, Solomon TPJ, Haus JM. Circulating soluble RAGE isoforms are attenuated in obese, impaired glucose tolerant individuals and are associated with the development of type 2 diabetes.Â American Journal of Physiology - Endocrinology and Metabolism. (August 15, 2017). doi:10.1152/ajpendo.00146.2017
Zuck J, Borges CR, Braun EJ, Sweazea KL. Chicken albumin exhibits natural resistance to glycation. Comparative Biochemistry and Physiology - B. 203:108-114, 2017. doi: 10.1016/j.cbpb.2016.10.003.