For World Diabetes Day
"Useful" subcutaneous fat and "pleasure hormone" that increases insulin sensitivity
November 14 is the day of the fight against diabetes, a disease that ranks seventh in the world among the causes of death. Scientists do not stop searching for new, more effective and safe methods of therapy for this disease. Among the promising developments are the protein adipsin, produced by subcutaneous fat; the hormone dopamine, which is synthesized in the "pleasure center" of the brain and regulatory microRNAs, with which adipose tissue cells "communicate".
Today, more than 400 million people suffer from diabetes in the world and, according to experts, by 2030 their number will reach half a billion. One of the main signs of diabetes mellitus is a persistent increase in blood glucose levels (hyperglycemia). There may be several reasons for this: diabetes mellitus unites a group of diseases with various mechanisms of pathology.
Every fifth patient suffers from type 1 diabetes, an autoimmune disease in which beta cells of the pancreas that produce the hormone insulin, which is involved in glucose metabolism, are destroyed. The only effective method of treating this disease is constant injections of insulin.
Among the little–known forms of diabetes is MODY-diabetes, or adult-type diabetes mellitus in young people. In this case, the development of hyperglycemia is caused by a mutation in a specific gene. Depending on the type of mutation, scientists divide MODY-diabetes into 14 subtypes, and each has its own optimal treatment methods. There is every reason to suspect this particular form of diabetes when it comes to a young patient with a normal body weight, in whose family there were diabetics in two or more generations. For such patients, conventional insulin therapy will not help. An accurate diagnosis in this case can only be made with the help of a molecular genetic examination. With early diagnosis of the disease in these patients, it is possible to compensate for carbohydrate metabolism disorders by correcting lifestyle and, if necessary, drug therapy.
But the most common type of diabetes mellitus is type 2 diabetes, in which insulin is produced, but the body loses the ability to respond to it. There is no "panacea" for this type of diabetes. For its treatment, various methods are used today, associated, for example, with the impact on different levels of regulation of carbohydrate metabolism. Insulin injections are also used, because over time, insulin-producing beta cells of the pancreas are affected in these patients.
However, the available medications are not always effective, moreover, their use is often accompanied by negative side effects, including those leading to too sharp a drop in glucose levels. Therefore, research continues, which opens up new, sometimes unexpected ways of treating type 2 diabetes mellitus.
For example, it turned out that glucose metabolism can be directly influenced by the "happiness hormone" dopamine, produced in the "pleasure center" of the brain associated with the work of the reward system. Scientists have found an increase in tissue sensitivity to insulin in patients with obsessive-compulsive disorder, who were treated with deep brain stimulation with electrical impulses in order to increase the release of dopamine. The significant role of this hormone in carbohydrate metabolism was confirmed in healthy volunteers, in whom the activity of dopamine synthesis was reduced with the help of drugs. Perhaps, over time, this phenomenon will be able to be used for the purposes of practical medicine.
By the way, dopamine can also affect carbohydrate metabolism indirectly, since its deficiency can lead to overeating due to insufficient "reward", i.e. lack of positive emotions. And here we come to one of the important conditions that often precede (and subsequently accompany) type 2 diabetes. This is a metabolic syndrome characterized by overweight and arterial hypertension. And adipose tissue is known to be involved in the development of various pathological processes, including disorders of carbohydrate metabolism.
There is still no consensus on the pathogenesis of this syndrome, and, consequently, there is no treatment, but most doctors recommend that such patients start with weight loss, for which they eat less and move more. But in serious cases, specific medications are prescribed.
By the way, adipocytes are the main cells of adipose tissue, they use universal intercellular "mail" to communicate with other cells. The latter is a microscopic vesicles-exosomes, in which, as in envelopes, various information molecules are packed, primarily small nucleic acids – regulatory microRNAs. It is known that the development of obesity and diabetes is associated with changes in the level of certain microRNAs, which was confirmed in experiments on genetically modified mice with the enzyme "turned off" necessary for the production of mature microRNAs. Transplantation of normal adipose tissue helped to restore in these animals not only the level of circulating microRNAs, but also glucose metabolism. If it is possible to find out how exosomes choose their cellular targets, they, along with microRNAs, can be used for targeted drug delivery and treatment of obesity and diabetes.
As for obesity itself, it's not so simple with it either. Recent studies have shown that subcutaneous fat, unlike fat on internal organs, can have a pronounced protective effect in the case of type 2 diabetes. It turns out that subcutaneous fat cells produce the protein adipsin, which helps protect the cells of the pancreas that secrete insulin. In experiments on mice with type 2 diabetes, high levels of this protein contributed to an increase in insulin levels and a decrease in glucose levels.
Using cell cultures, scientists were able to understand the mechanism of action of adipsin on human beta cells. It turned out that this protein activates one and suppresses another enzyme, on which the survival of beta cells depends. By directly suppressing the "killer" enzyme DUSP26 in human cell cultures and in experimental mice, the researchers saw that beta cells become healthier and produce insulin better.
Statistical analysis of the histories of 5.5 thousand people (participants in cardiovascular studies) showed that a higher level of adipsin in the blood was associated with a lower risk of diabetes, and the level of this protein was the lower the higher the level of adipsin. So both adipsin itself and DUSP26 enzyme blockers can be used to treat type 2 diabetes.
Among the latest promising developments is a drug based on a chimeric protein consisting of fragments of two other therapeutic proteins, which in themselves have negative side effects: an immune response can develop in the body to one of them, and inflammation to the other. The new protein is free from these disadvantages. In experiments on obese laboratory mice, its modification IC7Fc led to a decrease in body weight, improved glucose metabolism and increased insulin action. Clinical trials of the new drug are planned soon.
Of course, all of the above is the future of type 2 diabetes therapy. And in any case, it is clear that it is better to prevent the disease than to treat it. To the standard recommendations to monitor nutrition and engage in physical activity, the researchers add another, no less well–known, - do not smoke. And they do this not unfounded, but based on data on the relationship between nicotine addiction and the regulation of blood glucose levels. In experiments on genetically modified rats, it turned out that the Tcf7l2 gene, which regulates the activity of genes in the pancreas and liver, is also involved in regulating the response to nicotine in the brain region associated with the reward system. There is reason to believe that it is this gene that is "guilty" in connection with the use of nicotine and an increase in blood glucose levels, which leads to type 2 diabetes. If these results can be confirmed in human smokers, it can be assumed that the causes of the formation of not only type 2 diabetes, but also other diseases, such as cardiovascular, are associated with impaired interaction between the central and peripheral nervous system.
And while scientists are developing new, promising methods of treatment, doctors should choose from a wide range of available therapies the one that suits a particular person. The principle that "it is not the disease that needs to be treated, but the patient," proclaimed by Hippocrates, is as relevant as possible in our time.
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