Mechanism that could provide potential cure for diabetes identified
Washington: People develop diabetes because they don`t have enough pancreatic beta cells to produce the insulin necessary to regulate their blood sugar levels.
But now, researchers from UCLA`s Larry L. Hillblom Islet Research Center have discovered the underlying mechanism that could convert other cells in the body into the insulin-making cells, which could provide a potential cure for diabetes.
While the current standard of treatment for diabetes — insulin therapy — helps patients maintain sugar levels, it isn``t perfect, and many patients remain at high risk of developing a variety of medical complications.
Replenishing lost beta cells could serve as a more permanent solution, both for those who have lost such cells due to an immune assault (Type 1 diabetes) and those who acquire diabetes later in life due to insulin resistance (Type 2).
"Our work shows that beta cells and related endocrine cells can easily be converted into each other," said study co-author Anil Bhushan, an associate professor of medicine in the endocrinology division at the David Geffen School of Medicine at UCLA.
The researchers showed that chemical tags called "methyl groups" that bind to DNA — where they act like a volume knob, turning up or down the activity of certain genes — are crucial to understanding how cells can be converted into insulin-secreting beta cells.
They showed that DNA methylation keeps ARX, a gene that triggers the formation of glucagon-secreting alpha cells in the embryonic pancreas, silent in beta cells.
Deletion of Dnmt1, the enzyme responsible for DNA methylation, from insulin-producing beta cells converts them into alpha cells.
The findings suggested that a defect in beta cells`` DNA methylation process interferes with their ability to maintain their "identity." So if this "epigenetic mechanism," as the researchers call it, can produce alpha cells, there may be an analogous mechanism that can produce beta cells that would maintain blood sugar equilibrium.
"We show that the basis for this conversion depends not on genetic sequences but on modifications to the DNA that dictates how the DNA is wrapped within the cell," said Bhushan.
"We think this is crucial to understanding how to convert a variety of cell types, including stem cells, into functional beta cells," he added.
The study was published in the April issue of the journal Developmental Cell.