A new study explains the inefficacy of some diabetes drugs

Synchrotron light has been used for the first time to simulate damages due to oxidative stress on the aldose reductase protein with the aim of obtaining its activated form.

This form of the protein, related with some several diabetic complications, is insensitive to the drugs being developed, which hinders the treatment. ALBA researchers have shown that chemical changes suffered by the protein under oxidative stress are the cause of drugs inefficacy in the attempt to block aldose reductase. The team of the Synchrotron suggests a new method for drugs design considering the changes in proteins under oxidative stress, like the ones involved in diseases such as cancer, Parkinson or Alzheimer.
The protein aldose reductase has been explored as a drug target since the 1980s for its implication in diabetic complications. Now, the team of the ALBA Synchrotron, in collaboration with the Autonomous University of Barcelona, has shown the reason why some drugs against the effects of diabetes under development do not work in the attempt to block aldose reductase.
This protein has mainly detoxifying functions inside the cell but it can also transform glucose into a molecule called sorbitol. Under hyperglycemic conditions (high level of glucose in blood), this reaction increases much more and sorbitol accumulates, consuming antioxidant defenses. So, if hyperglycemia situation becomes chronic – like in diabetes -, there are unbalanced conditions inside the cell that lead to harmful oxidative stress environment.

Image: Isidro Crespo, Judith Juanhuix and Albert CastellvĂ­, at the biolaboratoy of the ALBA Synchrotron.