Scientists from the Stanford University School of Medicine, in Palo Alto, California, the United States have used a medicine in a mouse model to block the production of a substance that accumulates in the pancreas during the pre-symptomatic stage of theType 1 diabetes and that is essential for the development of the disease.
type 1 diabetes and extracellular matrix architecture
With the drug, currently used in Europe and Asia to treat pile -related spasms, they managed to prevent damage to insulin producing cells and the appearance of autoimmune disease.The results, described in an article published on Monday in the 'Journal of Clinical Research' magazine, suggest that it may be possible to prevent the appearance of type 1 diabetes in humans if a similar treatment begins before the cells producing cellsInsulin, or beta cells, are attacked by mistake by immune cells.
The study is the first to relate the progression of type 1 diabetes to changes in the architecture of the extracellular matrix, the network rich in carbohydrates and protein in which the cells that make up the tissues are embedded, according to one of the mainWork authors, Paul Bollyky, professor of infectious diseases.
pancreatic cells
Most pancreatic cells are dedicated to the manufacture and secretion of digestive enzymes, but the pancreas is also splashed from small groups of hormone -producing cells called islets.A human pancreas contains thousands of islets distributed throughout the organ and a pancreatic islet is formed by various types of cells, each generating a different hormone.Beta cells, for example, produce insulin.
"In type 1 diabetes, only beta cells are destroyed," Bollyky isthat is, they are infiltrated by immune cells.
"At the time a person begins to manifest the characteristic symptom of the disease, chronic hyperglycemia, about 90 percent of the pancreas beta cells are dead. The cause of the initial infiltration of immune cells in immune cells is not yet understoodthe pancreatic islets or the trigger for their transition from the mere passive presence to active aggression. "
Hiauluronic acid
In a 2014 study, the Bollyky team measured the levels of dozen substances in the extracellular matrix of human postmortem pancreatic tissue.A substance called hyaluronic acid was too abundant near the beta cells of the pancreas of people with type 1 diabetes, but it was only observed in the pancreatic tissue of patients who had been recently diagnosed, not patients who had lived with the disease for decades.
Hyaluronic acid is usually present in trace concentrations in the extracellular matrix that permeates all tissues, but hyaluronic acid levels are high at the site of an injury."If you twist the ankle or heel, the inflammation that is seen later is due to hyaluronic acid," Bollyky explains.This substance is prone to absorb water, causing the accumulation of liquid in the injured area, a cardinal characteristic of inflammation.
Bollyky points out that the absence of an increase in hyaluronic acid in the pancreatic islets of long -term patients does not meanMuch, since the beta cells of these people had long been defeated.But looking for excessive deposits of hyaluronic acid near pancreatic beta cells in recent cases was intriguing for researchers.
Bollyky and his colleagues tried to determine if this association was accidental or if the increase in the presence of hyaluronic acid actually played a causal role.Thus, they used a bioengineering laboratory mouse strain whose immune system is guaranteed to attack their beta cells of the pancreas.Essentially, one hundred percent of these mice eventually develop type 1 diabetes and always above approximately the same period of time, so it is easy to study the effects of experimental manipulation on the progression of the disease.
The scientists also observed another mouse strain often affected by a version of type 1 diabetes closer to the human form of the disease.But these mice are more difficult to study because only about half of them contract the disease and do it at variable rates.
Bollyky explains that in both strains, the hyaluronano accumulated in the pancreatic islets, but not in all of them, only in those where inflammatory immune cells had leverage.There was no excessive hyaluronano deposition in the heart tissue, lung or liver of mice, in line with the idea that the phenomenon occurs only in inflamed tissues.
The accumulation of hyaluronano associated with the islet eventually grew and began to decrease, analogous to the observations of the researchers in the cases of recent -type diabetes of recent appearance against the disease long established in its previous study of human tissue."We asked ourselves what would happen if we prevented accumulation, '
The drug was Hymecromone, or 4-methylumbeliferona (4-mu).Prescribed in many European and Asian countries for pain and spasms related to biliary calculation and sold by about 60 companies around the world for research purposes, 4-MU inhibits the synthesis of hyaluronic acid.It is cheap, it can be administered orally and, with more than four decades of use, it has a "very boring security profile": a very low rate of associated adverse events, says Bollyky.
"It is even approved in Europe for children," says this experts, adding that the American drug agency (FDA) has not authorized 4-MU for any indication in the United States.In the mice used in the study, as in people, there is a time window during which immune cells have infiltrated pancreatic islets but most beta cells are still intact.
When the researchers initiated the treatment with 4-MU before most mice cells had been annihilated, none of the mice developed hyperglycemia.The rodents who did not take 4-mu, did suffer from the disease and those who followed a 4-Mu regime, remained without diabetes for at least a year, but if this treatment stopped, they quickly became diabetics.
The tissue analysis revealed the continued presence of immune cells located near beta cells even in mice with 4-mu, but beta cells seemed normal, so immune cells had evidently refrained from attacking them.Scientists have also found reduced levels of hyaluronano in the pancreatic islets of mice treated with 4-MU, indicating that the drug was acting as expected.
Other experiments with rodents showed that the hyaluronanoPrevents the induction of a class of regulatory immune cells, known as regulatory T cells, whose work consists in controlling their companions aggressive immune cells and preventing them from harming healthy tissue.
