Feb. 16 (UPI) -- Researchers at Stanford University School of Medicine have found that pancreatic alpha cells in mice can be flipped to insulin-producing beta cells by blocking the expression of two genes.
"It is important to carefully evaluate any and all potential sources of new beta cells for people with diabetes," Dr. Seung Kim, Ph.D., professor of developmental biology and medicine and senior author of the study, said in a press release. "Now we've discovered what keeps an alpha cell as an alpha cell, and found a way to efficiently convert them in living animals into cells that are nearly indistinguishable from beta cells. It's very exciting."
Harini Chakravarthy, Ph.D., is the lead author of the study.
Alpha and beta cells in the pancreas are responsible for controlling the body's response to the rise and fall of blood glucose levels. Beta cells release insulin when glucose levels rise so sugar is stored for later use. Alpha cells release glucagon to stimulate the release of stored glucose when glucose levels fall.
"Transdifferentiation of alpha cells into insulin-producing beta cells is a very attractive therapeutic approach for restoring beta cell function in established type 1 diabetes," Andrew Rakeman, Ph.D., the director of discovery research at the Juvenile Diabetes Research Fund, or JDRF, said in a press release. "By identifying the pathways regulating alpha to beta cell conversion and showing that these same mechanisms are active in human islets from patients with type 1 diabetes, Chakravarthy and her colleagues have made an important step toward realizing the therapeutic potential of alpha cell transdifferentiation."
Researchers, building on a previous study in mice, showed that when beta cells are destroyed, about 1 percent of alpha cells in the pancreas start to look and act like beta cells slowly over time.
"What was lacking in that initial index study was any sort of understanding of the mechanism of this conversion," Kim said. "But we had some ideas based on our own work as to what the master regulators might be."
The team targeted the protein Arx, vital to the development of alpha cells, and DNMT1, which helps alpha cells "remember" how to be alpha cells by maintaining chemical tags on its DNA. Researchers generated a strain of lab mice unable to produce Arx or DNMT1 in alpha cells and found a rapid conversion of alpha cells into beta cells in the mice over seven weeks when both proteins were blocked.
"So the same basic changes may be happening in humans with type 1 diabetes," Kim said. "This indicates that it might be possible to use targeted methods to block these genes or the signals controlling them in the pancreatic islets of people with diabetes to enhance the proportion of alpha cells that convert into beta cells."
The study was published in Cell Metabolism.