The finding has been conducted by researchers at the Stanford University School of Medicine in the United States.
Researchers at the Stanford University School of Medicine, in the United States, have compared gene expression patterns in insulin producing cells and other pancreas cells of dozen donors who died between the ages of 6 months to 66 years.They found significant differences in gene expression patterns and DNA modifications between donors under 9 and those over 28 years old.
The results, which are published in Cell Metabolism, highlight the importance of two genes not previously involved in pancreatic function and show that the pancreas continues to develop and mature during the first decades of life.They can also have implications in current clinical trials on diabetes stem cell -based therapies.
"The study of human islet cells has been an important challenge in the field of diabetes investigation for decades because the pancreas digests itself essentially shortly after the death of a person," says the biology professor of the biology of the biology of the biology of the biology of the biology of the biology of the biology ofSeung Kim Development.
National Network
"We have developed a national network capable of eliminating and studying pancreatic fabric of organ donors from 6 months and up to 66 years within approximately a day and a half after death. This gave us an unprecedented opportunity to draw theChanges in gene expression during life, "adds Kim, main author of the study.
In the study, Kim, Arda and his colleagues identified two proteins never directly involved in pancreatic function, whose expression increases as a person ages.The increase in the expression of one of the proteins, Six3, in the insulin producing cells of younger donors has improved their ability to respond efficiently to the rise in glucose levels.
"The pancreatic islets, which are the insulin production sites, mature and change their function after a baby is born," we know, we believe that our findings suggest that this maturation process is prolonged for almost a decade. There has been aGrowing awareness among diabetes researchers that the development of human islets differs significantly from the development of islets in typical laboratory animals such as mice. "
Beta cells
The cells in pancreatic islets called beta cells are responsible for the modulation of the body's response to the rise and fall of blood glucose levels after a meal.When glucose levels rise, beta cells release insulin to give signals to cells throughout the body to store sugar for later use.
Type 1 diabetes is caused by the inability to produce insulin, while type 2 diabetes is caused by a combination of deficits in the body to respond and manufacture insulin.Both types have been related to the reduction of the number of beta cells insulin producers.
Although beta cells proliferate firmly during the first decade of life, this proliferation slows down drastically.Understanding the age -related signals generated by this slowdown could one day lead to new diabetes treatments.But it succeeds something more important than changes in the number of cells: rodent studies and in human fetal beta cells have shown that very young beta cell responses to blood glucose increases are direct compared to their more counterpartsMature
two human genes, key toBeta cells
Kim and his colleagues worked for more than six years to develop a multi-institutional collaboration to quickly collect pancreatic tissue and isolate and analyze cells of the islets of recently deceased donors.They also developed a unique cell classification technique to isolate islet cells from other cells in the pancreas.Once they had pure cell populations, they compared them to their gene expression patterns, as well as changes in the structure of DNA.
"We have identified hundreds of genes that are dynamically regulated in the beta cells of the islets during the trip from childhood to adulthood," Kim summarizes."One of the genes, Six3, is activated at some time around 9 years. We wonder if your expression could change the function of betas cells," he adds.
Powering the expression of Six3 in beta cells obtained from children under 9 years of age the capacity of the cells to secrete insulin in glucose was improved, according to the researchers.Six3 and a related gene, Six2, with a similar pattern of expression in human beta cells, encode proteins known as transcription factors that control the expression of many other genes in the cell.
Although they have not been directly involved in pancreatic function, genomic association studies have linked the presence of a mutation near genes to a deterioration of the ability to properly manage blood glucose levels on an empty stomach."This is a tempting link," Kim says. "It seems that genes whose expression changes between childhood and adulthood can be disproportionately associated with a greater risk of diabetes."
It is important to highlight that Six3 and Six2 are not expressed in mouse beta cells."This is why it is so important to study the human fabric," says Kim. "So far there has been any way to know the gradual changes that occur for a period of years."
