- Diabetes could be prevented thanks to a new molecule that has been discovered at the Salk Institute in the United States.
- This molecule is a lipid that is present in the body naturally and whose low levels seem to be related to the development of type 2 diabetes
- It could be a new way of treating type 2 diabetes
The image shows the glut4 protein that moves to the cell surface to help transport glucose from the blood to the cell after a meal.The left column shows the total amount of glut4 (green) in the cell and the right shows how much glut4 (red) it has joined the cell surface, a sign of positioning to facilitate the entry of glucose into the cell.
The first row, with no insulin present, shows very little glut4 in motion to the cell surface (up to the right, red).The second row, with a small amount of insulin present, shows some glut 4 on the cell surface (right center, red).The third row shows the same amount of insulin present along with a lipid Fahfa, resulting in much more glut4 on the cell surface, which increases the amount of glucose that can enter the cell (below right, red).
Researchers from the Salk Institute and the Beth Israel Deaconess (IDBMC) medical center in Boston have discovered a new kind of molecules in the fat and humans that protect against diabetes.
The administration of this new lipid (or fat) to mice with type 2 diabetes, reduces the high level of blood sugar as they have published in Cell magazine.The team has also found that the levels of these lipids are low in humans at high risk of diabetes, which suggests that these lipids can be used as therapy for metabolic disorders.
Some lipids, such as cholesterol, are associated with poor health.However, in recent years they have discovered that not all lipids (or fat) are bad such as omega-3 fatty acids found in the oil and fat of certain types of fish.The new discovered fats are hydroxy fatty acids or fahfas that showed lower levels in humans in the early stages of diabetes and higher in mice with diabetes resistance.
"On the basis of your biology, we can add fahfas to the reduced list of beneficial lipids," says Saghatelian Alana, professor at the Salk Institute in the Laboratories of the Clayton Foundation, and one of the main authors of the work."These lipids are surprising, since they can also reduce inflammation, which suggests that we could discover therapeutic opportunities in which these molecules can treat inflammatory diseases such as Crohn's disease, rheumatoid arthritis and diabetes."
Until now, Fahfas had not been detected in cells and tissues due to their low concentration.Using the latest mass spectrometry techniques, Saghatelian and Barbara Kahn Vice President of the Department of Medicine of IDMC and the other main author of the study, the Fahfas discovered when they examined the fat of a diabetes resistant mouse model designed by Kahn.
"We have designed these mice to have more than one sugar transporter, called GLUT4 in their fat, since we had shown that when the levels of this conveyor are low, people are prone to develop diabetes," says Kahn.When examining how this sugar transporter could help protect against diabetes, the equipment realized the greatest synthesis of fatty acids in mice that had improved insulin activity (and therefore were less likely to develop diabetes).The team collaborated to find out whatlipids were involved.
"While many of the other lipids were essentially the same between normal mice and these diabetes resistant mice, we saw the lipids Fahfa elevated to the tenth powerful power in mice that were resistant to diabetes, highlighting very clearly as a great change,"Saghatelian says.“After that, we have elucidated its structures using a combination of mass spectrometry and chemical synthesis.Basically discovered a new class of molecules that use these techniques. "
Once fahfas were identified as the lipid that made the difference between normal mice and these diabetes resistant mice, they found something more important: when mice eat fahfas, blood sugar levels decreased and insulin levelsThey rose, indicating the potential therapeutic value of Fahfas.
To determine if fahfas are also relevant in humans, the team measured the Fahfa levels in human beings that are insulin resistant (a condition that is often a precursor of diabetes) and it was found that their fahfa levels were lowerIn fat and blood, which suggests that changes in FAHFA levels can contribute to diabetes.
"The highest levels of these lipids seem to be associated with positive results in mice and human beings," says Kahn, who is also a professor at Harvard Medical School.“We show that lipids work through multiple mechanisms.When blood sugar increases, for example after a meal, lipids quickly stimulate the secretion of a hormone that indicates to the pancreas that insulin should secrete.In addition, these new lipids also directly stimulate the absorption of sugar in the cells and reduce inflammatory responses in adipose tissue and throughout the body. ”
These combined effects make the therapeutic potential of lipids huge, researchers say.Apart from that there are low levels in a wide range of vegetables, fruits and other foods, fahfas are also produced and degraded inside the body.Potentially, the new drugs could point to the tracks that synthesize or degrade lipids to control Fahfa levels.
In the new study, the team also identified the cell receiver to which Fahfas are binding, called GPR120, to control the amount of glucose is absorbed by fat cells.The team thinks that the increase in Fahfa body levels can also be a way to activate GPR120 to treat or prevent diabetes.
"This work can suggest that changes in Fahfa levels are a new mechanism in diabetes that was underestimated before because these lipids were not known," says Saghatelian."We hope this work points to new therapies that could promote the shape of the blood sugar management body itself."
"Because we can detect low Fahfa levels in blood before a person develops diabetes, these lipids could serve as an early score of diabetes risk," adds Kahn."We want to prove if lipid restoration before diabetes develops could potentially reduce risk or even prevent disease."