Diabetes comes at night
Pyotr Smirnov, "Newspaper.Ru»
The "nocturnal" hormone melatonin can provoke the development of type 2 diabetes in those who have a mutant form of a receptor for it. Such receptors are no more or less sensitive to the hormone, but there are too many of them on the surface of the cells synthesizing insulin. As a result, it becomes difficult for the body to control glucose levels.
The beautiful word "chronobiologist" can still be called only scientists, but not doctors – unfortunately for millions of people around the world suffering from insomnia. Until today, these unfortunate people had to turn to a neurologist for advice. But in the near future, with a similar problem, it will be possible to come to a hormone specialist, an endocrinologist.
Three research groups have found a genetic link between the development of diabetes, obesity and circadian rhythm disorders.
The material basis of this connection is the hormone melatonin, or rather the MTNR1B receptor (melatonin receptor 1beta) to it, located on the surface of many cells of our body. Including, as separately shown by Leif Grop and his colleagues in one of the three mentioned works, and on the cells of the islets of Langerhans responsible for the synthesis of insulin.
Melatonin is the main hormone of the pineal body of the brain (epiphysis). The circadian rhythm depends on it. Changes in melatonin concentration have a noticeable diurnal rhythm in the pineal body and in the blood, usually with high levels of the hormone during the night and low levels during the day. The maximum values of melatonin in the blood are observed between midnight and 4 a.m.
The main physiological effect of melatonin is to inhibit the secretion of gonadotropins. In addition, the secretion of other tropic hormones of the anterior pituitary gland – corticotropin, thyrotropin, somatotropin - decreases, but to a lesser extent.
The secretion of melatonin is subordinated to the circadian rhythm, which, in turn, determines the rhythmicity of gonadotropic effects and sexual function. The synthesis and secretion of melatonin depend on the illumination – excess light inhibits its formation, and a decrease in illumination increases the synthesis and secretion of the hormone. In humans, night hours account for 70% of the daily production of melatonin.
One of the main actions of melatonin is the regulation of sleep. With age, the activity of the pineal gland decreases, so the amount of melatonin decreases, sleep becomes shallow and restless, insomnia is possible. Melatonin helps to eliminate insomnia, prevents violation of the daily regime of the body and biorhythm. Insomnia and lack of sleep give way to healthy and deep sleep, which relieves fatigue and irritability. Melatonin affects the activity of the endocrine glands, for example, regulates the menstrual cycle in women, and also stimulates sexual life and slows down the aging process.
Although the true cause-and-effect relationship can be disputed, scientists believe that melatonin secreted by the pineal body of the brain controls the release of insulin, or rather slows it down, regardless of the concentration of glucose in the blood. It has long been established that the concentration of melatonin and insulin in the blood changes "in the opposite phase": the level of insulin increases during the day even on an empty stomach, and it falls at night when melatonin dominates, partly determining the normal operation of the circadian rhythms of our body.
And if the work of the melatonin cycle is disrupted, this will inevitably lead to a violation of glucose regulation. Regardless of which way – day or night – the scales will tilt, sooner or later this will lead to the development of type II diabetes.
Type 2 diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia (increased blood glucose), which is the result of impaired insulin secretion or mechanisms of its interaction with tissue cells (definition of the World Health Organization 1999).
This type of disease is caused by a decrease in the sensitivity of tissues to the action of insulin (insulin resistance), which is synthesized in normal or even increased amounts at the initial stages of the disease.
Diet and weight loss of the patient in some cases help to normalize the carbohydrate metabolism of the body and reduce glucose synthesis at the liver level. However, with the course of the disease, insulin secretion by pancreatic cells decreases, which makes insulin injections necessary.
Type 2 diabetes accounts for 85-90% of all forms of diabetes, most often develops in people over 40 years old, and is usually associated with obesity. The disease proceeds slowly. It is characterized by secondary symptoms, ketoacidosis rarely develops. Over time, complications such as micro- and macroangiopathy, nephro- and neuropathy, retinopathy and others develop.
Diabetes mellitus is manifested primarily by an increase in blood glucose levels, a decrease in the ability of tissues to capture and utilize glucose and an increase in the mobilization of alternative energy sources – amino acids and free fatty acids.
A high level of glucose in the blood and various biological fluids causes an increase in their osmotic pressure. As a result, osmotic diuresis occurs (increased loss of water and salts through the kidneys), leading to dehydration (dehydration) of the body and the development of deficiency of sodium, potassium, calcium and magnesium cations, chlorine anions, phosphate and bicarbonate.
A patient with diabetes mellitus develops increased thirst, frequent profuse urination, weakness, increased fatigue, dryness of the mucous membranes despite drinking plenty of water, muscle twitching, cardiac arrhythmias and other manifestations of electrolyte deficiency.
The MTNR1B receptor occurs in humans in several species. The owners of one of the variants are distinguished by a mutation in the rs10830963 position on the 11th chromosome, found in 30% of Europeans. Grop found that such receptors have the same sensitivity to melatonin, but there are disproportionately many of them on the surface of cells synthesizing insulin. As a result, the same concentration of melatonin in the blood slows down the release of insulin much more strongly. This slows down the utilization of glucose by tissues, its level increases, and with it the risk of developing diabetes increases.
In total, almost 40 thousand healthy Finns and Swedes took part in the study at the time of the start of work. Observation of them for several years has shown that the owners of the mutation have an 11% higher risk of getting type 2 diabetes.
Gonzalo Abecasis and co-authors of the second publication in Nature Genetics focused on the same mutation, but traced how the number of mutant copies in the genotype affects glucose levels and the risk of diabetes. Since each person carries two sets of chromosomes (from the father and mother), there may not be such copies at all, there may be one, or there may be two.
As Abecasis and his colleagues have shown, each copy leads to an increase in glucose levels by about 1.5%. At the same time, the probability of getting type 2 diabetes increases by 5-12% for each copy! The authors attribute a significant spread to the "broad national representation" of the sample of almost 37 thousand Europeans.
Approximately the same results were obtained by Philippe Froguel and his colleagues, who studied exclusively the French for 9 years. However, they considered another mutation – in the rs1387153 position.
Although the authors of the last two papers have not studied the intracellular mechanism of diabetes development in detail, it is possible that it may be much simpler than in the first one. Doctors have repeatedly noticed that sleep disorders are often associated with depression and obesity, as well as vice versa. And obesity is the main risk factor for type 2 diabetes, so circadian rhythm disorders, whether they are associated with melatonin or not, can themselves increase the risk of developing diabetes.
Whether it will be possible to develop a new way of preventing and treating diabetes with the help of these findings is still unknown, but the need to comply with the regime has once again been confirmed.
Portal "Eternal youth" www.vechnayamolodost.ru08.12.2008