More than five years ago, Dr. Lawrence C.B. Chan and colleagues in his Baylor College of Medicine laboratory cured mice with type 1 diabetes by using a gene to induce liver cells to make insulin.
"Now we know how it works," said Chan, director of the federally designed Diabetes and Endocrinology Research Center at BCM and chief of the division of endocrinology in BCM's department of medicine. "The answer is adult stem cells."
A gene called neurogenin3 proved critical to inducing cells in the liver to produce insulin on a continuing basis, said Chan and Dr. Vijay Yechoor, assistant professor of medicine-endocrinology and first author of the report that appears in the current issue of the journal Developmental Cell . The research team used a disarmed virus called a vector to deliver the gene to the livers of diabetic mice by a procedure commonly known as gene therapy.
"The mice responded within a week," said Yechoor. The levels of sugar in their blood plummeted to normal and stayed that way for the rest of their normal lives.
The quick response generated more questions as did the length of time that the animals stayed healthy.
They found that there was a two-step response. At first, the neurogenin3 gene goes into the mature liver cells and causes them to make small quantities of insulin – enough to drop sugar levels to normal, said Yechoor.
"This is a transient effect," he said. "Liver cells lose the capacity to make insulin after about six weeks."
However, they found that other cells that made larger quantities of insulin showed up later, clustered around the portal veins (blood vessels that carry blood from the intestines and abdominal organs to the liver).
"They look similar to normal pancreatic islet cells (that make insulin normally)," said Yechoor.
They found that these "islet" cells came from a small population of adult stem cells usually found near the portal vein. Only a few are needed usually because they serve as a safety net in case of liver injury. When that occurs, they quickly activate to form mature liver cells or bile duct cells.