One molecule, many more insulin-producing cells to treat diabetes, says Pitt team

July 28, 2010

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 to replicate, as well as important differences between mouse and human beta cells that could influence how these approaches are best used to treat , which is caused by insufficient leading to abnormal .

"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 authorAndrew 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 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."

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, Dr. Stewart noted.

He and his colleagues continue to explore many other regulatory proteins that could play a role in encouraging or thwarting beta cell replication.

Related Stories

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.