The missing link in the pathogenesis of diabetes has been found
The third most important hormone associated with type 2 diabetes has been discovered
Nanonews Network based on Johns Hopkins Children's Center materials:
Johns Hopkins Scientists Identify Third Critical Hormone in Type 2 Diabetes
Working with samples of mouse and human blood and liver, scientists from the Johns Hopkins Children's Center found that the most important player in the development of type 2 diabetes is one of the liver proteins, never previously suspected in connection with this disease. Recall that type 2 diabetes mellitus is one of the leading causes of heart disease and stroke, as well as kidney, nervous system and eye diseases.
The results of this study, published in the journal Cell Metabolism (Woo-Jin Song et al., Glucagon Regulates Hepatic Kisspeptin to Impair Insulin Secretion), show that the hormone kisspeptin 1 (kisspeptin 1, or K1) – still known for its role in regulating puberty and fertility – slows down the production of insulin, a hormone responsible for blood sugar levels, and thus stimulates the development of type 2 diabetes.
According to scientists, they managed to find the missing link in the development of this disease. To maintain a normal blood sugar level, two hormones, glucagon and insulin, must work synchronously. Secreted when sugar levels drop, glucagon causes the liver to release its strategic stores of glucose into the bloodstream. When sugar levels rise, insulin acts as an "antidote" to glucagon, helping the body lower blood sugar levels by transporting it to organs and tissues as fuel. In type 2 diabetes, pancreatic cells secrete too little insulin, or do not secrete it at all, which leads to a dangerous rise in blood sugar.
Patients with type 2 diabetes or with an early form of this disease, known as prediabetes, have abnormally high levels of the sugar-boosting hormone glucagon, even in the presence of insulin and even when the body does not need sugar. Researchers have long wondered whether abnormal glucagon levels affect insulin-secreting pancreatic cells. It is generally accepted that chronically elevated levels of glucagon and sugar have a constant effect on the pancreas, and its overloaded beta cells gradually reduce insulin synthesis until they completely stop its production.
However, new data suggest that pancreatic cells do not just get tired – their function is directly suppressed by kisspeptin 1. In particular, the researchers found that the liver, stimulated by high levels of glucagon, releases K1 into the bloodstream. Then K1 enters pancreatic beta cells, where it suppresses insulin secretion.
"The data we have obtained suggests that glucagon gives orders, and K1 executes these orders, and, apparently, is the main reason for the decrease in insulin secretion observed in type 2 diabetes," says the head of the study, endocrinologist Mehboob Hussain, MD. "Glucagon and insulin have never been explained everything. There has always been something missing, and, in our opinion, kisspeptin 1 is a very good candidate for the role of this missing component. All our data points to this."
In one series of experiments, the researchers fed a group of mice with high-calorie food. As expected, the mice developed diabetes, insulin production decreased, and the level of K1 in their blood increased dramatically. When scientists chemically modified the liver of diabetic mice, making it unable to synthesize K1, insulin levels returned to normal. The researchers then created mice whose pancreatic cells had no receptors for the hormone K1. These mice, even those on a high-fat diet, maintained normal insulin production and blood sugar levels. In other words, the missing receptor of the hormone kisspeptin made the insulin-secreting cells of these animals insensitive to the action of K1.
In addition, the researchers found that K1 levels were markedly elevated in blood and liver samples of patients with type 2 diabetes. Moreover, when they exposed mouse pancreatic cells to K1-rich blood plasma obtained from patients with type 2 diabetes, insulin synthesis in these cells decreased.
Glucagon stimulates the liver's production of kisspeptin 1 (K1) and gluconeogenesis. K1 suppresses glucose-stimulated insulin secretion by beta cells. An increased level of glucagon in the blood in diabetes reduces insulin secretion with the help of hepatic kisspeptin 1. In mice with diabetes, the knockdown of the Kiss1 gene in the liver normalizes glucose-stimulated insulin secretion and glycemia. (Fig. Cell Metabolism)The identification of K1 as a key player in the development of diabetes, the researchers believe, provides a new potential therapeutic target that may lead to the development of drugs that restore the function of insulin-secreting cells.
Currently, diabetes therapy is based on injections of synthetic insulin. However, restoring the natural production of insulin, theoretically, cures diabetes, and not just alleviates its symptoms.
Dr. Hussain and his colleagues have already identified a hormone-like substance that blocks the K1 receptor in mouse pancreatic cells. Now the researchers plan to find out whether this receptor blocker can restore the function of human pancreatic cells.
The existence of K1 makes evolutionary sense and may explain why diabetes is an ancient disease found in different species. Dr. Hussein and his colleagues believe that K1 could have developed to perform the function of suppressing the effect of insulin and preventing a sharp drop in sugar levels in "fight or flight" situations (that is, when the body reacts to stress).
"When an animal engages in a fight or tries to escape from a predator, sugar is a vital fuel," explains Dr. Hussain. "High insulin levels after eating can lead to dangerously low blood sugar levels, which will make the animal weak and vulnerable. Thus, our theory says that K1 is a protective mechanism that suppresses the hypoglycemic effects of insulin in such situations when there is a life-and-death struggle."
Type 2 diabetes, closely associated with a diet high in fat and sugar and a sedentary lifestyle, is the predominant form of this disease, which accounts for more than 90 percent of all its cases. If earlier type 2 diabetes was observed mainly in middle-aged and elderly people, now it is increasingly developing in young people and even children, which scientists explain by the epidemic of obesity in developed countries.
Portal "Eternal youth" http://vechnayamolodost.ru07.04.2014