How are fasting, cancer and diabetes interrelated
Scientists at the Salk Institute for Biological Research (San Diego), working under the leadership of Rubin Shaw, claim that they know what mechanisms many, and maybe all organisms use to conserve energy in conditions of lack of nutrition.
The authors demonstrated that if mammalian cells feel that the reserves of glucose and other nutrients are running out, they suppress the activity of the raptor protein, which leads to a slowdown in their growth. This study not only sheds light on the survival strategy used by both simple and complex organisms, but also reveals an unexpected relationship between cancer and diabetes.
Experts knew that if this scheme is violated, starving cells continue to divide until they consume all resources and die. The authors wanted to find out whether all the components of this mechanism have been identified.
In experiments on mouse and human cells, they found that if cells are cultured under conditions of nutrient deficiency, the AMPK enzyme is activated, attaching a phosphate group to the raptor protein. In this case, not only this protein is inactivated, but also the mTOR protein that stimulates cell growth, the functioning of which depends on the activity of the raptor protein. As a result, cell division stops, and they switch to an energy-saving mode that continues until conditions improve.
Previously, the authors demonstrated that the activity of the AMPK enzyme regulates the protein LKB1, which is important from a biochemical point of view, known as a tumor growth suppressor. Loss of functionality contributes to the formation of benign hamartoma tumors and some types of lung and colon cancer. Most of these tumors are characterized by high levels of unregulated activity of the mTOR protein.
As part of the latest work, the authors tried to find out how LKB1 mutations lead to the development of cancer. In search of unknown components of this mechanism, they analyzed a collection of protein fragments phosphorylated by the AMPK enzyme and identified a raptor protein suitable for this role. An interesting fact is that a small fragment of this protein has remained unchanged in a huge number of species, ranging from slime molds (myxomycetes) to humans.
The results of biochemical studies have shown that AMPK does directly phosphorylate raptor in an energy crisis, which reduces the activity of mTOR and prevents the division of starving cells and their death from exhaustion.
From a clinical point of view, the results of this work are also of great importance, because the drug metformin, widely used to reduce blood sugar levels, activates AMPK. Thus, the LKB1/AMPK mechanism provides a molecular relationship between diabetes and cancer and explains the increased risk of developing malignant tumors characteristic of patients with type 2 diabetes.
The authors plan to continue their research and, first of all, get answers to the following questions: "Can mutations of the components of the LKB1/AMPK mechanism underlie the development of both pathologies under consideration"? and "Can any antidiabetic drugs help in the fight against malignant neoplasms"?
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
29.04.2008