With a single stimulatory molecule, human insulin-producing beta cell replication can be sustained for at least four weeks in a mouse model of diabetes, according to researchers at the University of Pittsburgh School of Medicine in Diabetes, a journal of the American Diabetes Association.
They also found several cocktails of molecules that drive human beta cells to replicate, as well as important differences between mouse and human beta cells that could influence how these approaches are best used to treat diabetes, which is caused by insufficient insulin production leading to abnormal blood sugar levels.
"Our team was the first to show that adult human beta cells can be induced to proliferate or grow at substantial rates, which no one thought possible before," said senior author Andrew F. Stewart, M.D., professor of medicine and chief of the Division of Endocrinology and Metabolism, Pitt School of Medicine. "Now our effort has been to unravel these regulatory pathways to find the most effective strategy that will allow us to treat - and perhaps cure - diabetes by making new insulin-producing cells."
In a series of experiments, lead author Nathalie M. Fiaschi-Taesch, Ph.D., assistant professor of endocrinology, and the team discovered that combining elevated amounts of the regulatory molecules cdk4 or cdk6 with a variety of D-cyclin proteins, particularly cyclin D3, stimulates human beta cell replication in test tubes.
"We didn't expect cyclin D3 to ramp up beta cell replication so strongly when it was used with either cdk4 or cdk6," Dr. Fiaschi-Taesch said. "There was no known role for cyclin D3 in human beta cell physiology."