In the study published today in the Journal of Clinical Investigation (JCI), one of the journals with highest impact in experimental medicine, the researchers associate the activity of the DOR protein with muscle atrophy and point to DOR as a plausible target against which to develop a drug to prevent muscle deterioration in certain diseases.
DOR (Diabetes- and Obesity-regulated gene), also known as TP53INP2, is a protein involved in autophagy, a quality control process that ensures cells stay healthy. The researchers have found that increased DOR expression in the muscle of diabetic mice leads to enhanced autophagy, which in turn favours the loss of muscle mass in these animals.
The advantage of developing a DOR inhibitor is that autophagy, a process necessary to keep cells healthy, would not be completely blocked in the absence of this protein. DOR is not essential for autophagy, but acts more as an accelerator. Thus, the inhibition of DOR would only partially reduce autophagy as other molecules involved would exert their activity normally, thus maintaining the levels of autophagy in a beneficial range for cells.
"If we could treat patients with sarcopenia and cachexia, or people at risk of these conditions, using a drug to inhibitor DOR then we would be able to stop or prevent muscle wasting," explains the expert in diabetes and obesity Zorzano, head of the "Heterogenic and Polygenic Diseases" lab at IRB.
"We are showing pharmaceutical researchers a new possible therapeutic target for two diseases that seriously impair the quality of lives of those who suffer from them," says the scientist.
An answer to why type 2 diabetic patients lose less muscle than those with type 1
The study also solves a biomedical enigma related to diabetes. Physicians did not understand why patients with type 2 diabeteswho become resistance to insulin or have very low levels of this hormoneare able to maintain muscle mass
|Contact: Sònia Armengou|
Institute for Research in Biomedicine (IRB Barcelona)