An experiment on older mice will help improve people's quality of life

Scientists from Russia and Sweden are working under a grant from the Russian National Research Foundation to investigate the causes of metabolic disorders that lead to type 2 diabetes mellitus (DM2). To find a switch that increases or decreases the sensitivity of cells to insulin, including during exercise, physiologists modeled this disease in mice. Such an experiment will be conducted for the first time in rodents whose age corresponds to 50-80 years of human life. The relationship between metabolic syndrome and sarcopenia will also be studied. The data obtained will help develop new approaches to treating these ailments and improve the quality of life for people of pre-retirement and retirement age.

Almost 90% of diabetes patients have the second type, in which the patient produces insulin but the body cannot use it effectively. DM2 develops slowly and imperceptibly, and many people are diagnosed only after the onset of complications.

- In general, the mechanism of the disease’s development is known - a failure occurs at the protein level, where the delivery of glucose to the muscles is ensured, - explains Leonid Kapilevich, head of the Department of Sports and Health Tourism, Sports Physiology, and Medicine at the Faculty of Physical Education. - Nobody knows why the transporter protein breaks. However, a number of observations show that these violations are reversible, because physical activity gives a positive effect. Our task is to find the key that will help glucose pass through the cell membrane into the muscles and start the sugar utilization process.

To find out, scientists set up an experiment on mice. Under the previous project, they modeled DM2 in rodents, using a special food. For 16 weeks, the mice developed obesity and increased sugar and insulin levels - all the symptoms characteristic of DM2 appeared. Then the rodents were provided with daily exercise - training on a treadmill specially created for the experiment. The scientists found that the group that ran in the morning had a lower glucose level, and the insulin in the group trained in the evening fell faster. In mice, the diurnal rhythm is reversed, therefore, for humans, the data obtained should be considered in reverse.

- This project helped us to continue the previous research, - says Leonid Kapilevich. - The scientific leader of the new project is Alexander Chibalin (Karolinska University, Sweden), a well-known specialist in skeletal muscle physiology. Now we are investigating proteins, RNA, and other compounds in animals that were involved in the experiment. The comparative analysis will help to identify changes that occurred in the development of diabetes and during the normalization of indicators. Thus, we expect to establish the factor that underlies the violation of the regulatory mechanism and leads to the development of this serious illness.

According to Leonid Kapilevich, currently the treatment of DM2 is carried out mainly with a strict diet, feasible physical exertion, and some drugs that lower sugar. TSU scientists aim at obtaining fundamental data that can be used to create fundamentally new drugs that stimulate the launch of natural sugar utilization in the patient's body.

To learn as much as possible about the mechanism of DM2 development , scientists - for the first time in the study of diabetes - will conduct an experiment on adult mice whose age corresponds to 50-80 years of human life. The difficulty lies in the fact that the standard age of rodents from the pure lines on which research is carried out is two months. For these studies, the animals will grow to 8 months of age. After that, using special nutrition, they will simulate diabetes, then several groups will start training. As a result, the scientists will be able, first, to clarify the molecular mechanisms of muscle insulin immunity formation and reduction of the ability to absorb glucose from the blood, and second, to find out how exercise can reverse this process.

In parallel, the researchers will establish the relationship between metabolic syndrome and the development of sarcopenia - atrophy of skeletal muscles that leads to physical weakness.

- The process of muscle tissue loss and replacement with connective tissue begins already after age 35, and the main problems begin at 50-60 years old, - specifies Leonid Kapilevich. - This problem is very acute for humanity, sarcopenia is one of the main factors reducing quality of life in the elderly. There is scattered evidence that not only age is to blame, but that metabolic disorders also play an important role in this pathology. We want to test how strong this interconnection is. If our hypothesis is correct, then we can find new ways to manage the metabolic syndrome, which will help us delay or prevent sarcopenia.