The vicious circle of diabetes
Diabetes affects 415 million people worldwide. In the UK, this disease has been diagnosed in almost 5 million people, it costs the National Health Service about 10 billion pounds annually. About 90% of cases are type 2 diabetes, which is characterized by the inability of pancreatic beta cells to produce insulin, which leads to chronically elevated blood glucose levels. Type 2 diabetes mellitus usually manifests itself in older adulthood, and by the time of diagnosis, up to 50% of beta cell function has already been lost.
Hyperglycemia is known to slow down the mitochondria of pancreatic beta cells and reduce insulin production, but the mechanism of this effect was unclear.
The concentration of glucose in the blood should be kept in a narrow range. Low glucose levels lead to loss of consciousness, as the brain lacks "fuel". A high concentration of glucose in the blood is also dangerous, because it is complicated by serious diseases – retinopathy, nephropathy, peripheral neuropathy and heart disease. Insulin, secreted by beta cells of the pancreas when blood glucose levels rise, is the only hormone that can reduce glucose concentration. In type 2 diabetes, the number of beta cells does not decrease (unlike type 1 diabetes), but the insulin content in them is reduced.
Researchers have suggested that prolonged hyperglycemia triggers a vicious circle in which an increase in blood glucose leads to damage to beta cells and a decrease in insulin secretion, which causes an even greater increase in glucose and a further decrease in beta cell function. To break this cycle, it is necessary to know exactly how hyperglycemia disrupts the function of beta cells.
A group of researchers from the University of Oxford, using animal models of diabetes and human beta cells, for the first time showed that glucose metabolites, and not glucose itself, are the cause of the inability of beta cells to secrete insulin in type 2 diabetes. They also demonstrated that beta cell damage caused by hyperglycemia can be prevented by slowing down the rate of glucose breakdown.
High blood glucose levels accelerate carbohydrate metabolism in beta cells, which leads to intracellular accumulation of glucose metabolites. They directly and indirectly (by suppressing enzymes) inhibit the tricarboxylic acid cycle. This leads to a decrease in the production of the energy molecule ATP in the mitochondria of beta cells. Without energy, weakened beta cells become "blind" to glucose and no longer respond to an increase in blood glucose levels by releasing insulin.
Thus, in order to break the vicious circle, it is necessary to slow down the absorption of glucose, although at first glance it does not seem logical. Researchers have shown that blocking the enzyme glucokinase, which regulates the first stage of glucose metabolism, can prevent the described changes and keep insulin secretion at normal levels in chronic hyperglycemia. Based on glucokinase inhibitors, new strategies for the treatment of type 2 diabetes may appear.
Article by E.Haythorne et al. Altered glycolysis triggers induced mitochondrial metabolism and mTORC1 activation in diabetic β-cells is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Oxford: Key cause of type 2 diabetes uncovered.