In type 2 diabetes, cells become insensitive to the hormone insulin and stop absorbing glucose from the blood. This leads to widespread biochemical and physiological disturbances throughout the body – it is difficult to find an organ that is not affected by diabetes. Due to abnormalities in metabolism, mitochondria – cellular organelles that provide energy for the cell – fail. When it affects the heart, diabetic cardiomyopathy develops, one of the most dangerous complications of diabetes.
Employees of the Institute of Theoretical and Experimental Biophysics (ITEB) of the Russian Academy of Sciences, studying the state of mitochondria in the heart and skeletal muscles in diabetes, suggest protecting them with the drug alisporivir. It inhibits the activity of the protein cyclophilin D. All cyclophilins are quite specific enzymes that change the spatial structures of chemical bonds between amino acids in other proteins; in other words, they carry out an isomerization reaction. Cyclophilins are very numerous and very important for the cell, although the specific functions of each depend on where the particular cyclophilin works. So, cyclophilin D is located in mitochondria: here the formation of a special pore in mitochondrial membranes depends on it, which causes the destruction of mitochondria. This time opens in cases when the cell is under severe stress and it is easier for it to die carefully than to stay alive and harm others.
However, the time in mitochondria is not always so necessary; it happens that both mitochondria and the cell as a whole could continue to live and work, and instead they die. Alisporivir, which suppresses the activity of cyclophilin D, helps to avoid unnecessary death. In two articles in International Journal of Molecular Sciences and Biology the researchers describe how alisporivir prevents mitochondrial destruction and cardiac and skeletal muscle cell death in diabetes. When given to mice that were kept on a fatty diet and thus injected into a diabetic state, in such mice, alisporivir helped the cells absorb glucose from the blood and normalized the work of the heart, which began to suffer from diabetic complications. The results obtained allow us to conclude that alisporivir can be used in the complex therapy of diabetes mellitus.
This work was supported by the Russian Science Foundation.
According to the press service of ITEB RAS
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