A new study has said that a single stimulatory molecule, along with other regulatory proteins, could play a role in encouraging or thwarting insulin-producing beta cell replication, which in turn could treat diabetes.
Researchers at the University of Pittsburgh School of Medicine found that a stimulatory molecule could sustain human insulin-producing beta cell replication for at least four weeks in a mouse model of diabetes.
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. 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," said senior author Dr. Andrew F. Stewart, professor of medicine and chief of the Division of Endocrinology and Metabolism, Pitt School of Medicine.
In a series of experiments, lead author Dr. Nathalie M. Fiaschi-Taesch, 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. There was no known role for cyclin D3 in human beta cell physiology," said Dr. Fiaschi-Taesch.
Cyclin D2 is present in and essential for rodent beta cell replication and function, but the team showed that molecule is barely detectable in human cells, and beta cell replication could be sustained for at least four weeks in a model in which mice were transplanted with human beta cells engineered to overproduce cdk6.
Blood sugar normalized in the diabetic mice transplanted with surprisingly small numbers of human beta cells, indicating that the cells functioned properly to produce needed insulin.
Mice don't appear to make cdk6 naturally, but they do have cdk4 and cyclins D1 and D2, so standard rodent studies of beta replication might have led scientists to pursue the wrong molecules in their quest to stimulate human beta cell replication, noted Stewart.
The researchers continue to explore many other regulatory proteins that could play a role in encouraging or thwarting beta cell replication.
The study is published in Diabetes, a journal of the American Diabetes Association.