Newfound hormone holds hope for diabetes treatment

Dan Vergano, USA TODAY

A newly discovered mouse hormone may open the door to better treatment for diabetes, researchers suggested Thursday.

The hormone, called betatrophin, triggers the growth of pancreatic "beta" cells lost or ineffective in diabetes. Insulin is produced by beta cells in the pancreas.

Diabetes afflicts more than 25 million people nationwide, according to the American Diabetes Association. It is a condition that causes high blood sugar that can lead to heart disease, kidney failure and blindness.

In the journal Cell, a team led by Harvard's Peng Yi reports that betatrophin can produce a roughly seventeenfold increase in these cells, and its increase may partly explain the rapid growth of these cells seen during pregnancy to feed developing fetuses in mammals, including people.

"This is really an amazing discovery. Hormones with this kind of effect aren't discovered very often, and this opens a whole new pathway to treating diabetes," says diabetes expert Jake Kushner of the McNair Medical Institute at Baylor College of Medicine in Houston, who was not part of the study team. He cautioned that the hormone's effects, which the study team sees as isolated to beta cells, need to be thoroughly investigated in animal studies for safety.

The hormone was discovered almost by accident, as the Harvard team investigated a research compound that basically recreates what happens in diabetes. The compound short circuits the release of insulin in response to increasing blood sugar. When that happened to the mice in the study, their production of the hormone betatrophin ramped up and spurred the growth of insulin producing cells. Diabetics often need daily insulin injections to compensate for the condition, where in Type 2, or adult-onset diabetes, the most frequent kind, beta cells stop producing enough insulin, and in juvenile diabetes, or Type 1, about 10% of cases, beta cells have died.

"Of course, we are a long way from a treatment. But if this could be used in people, what I think it could mean eventually is that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month," says study senior author Doug Melton of the Harvard Stem Cell Institute, in a commentary provided by the university.

Melton is best known as a prominent human stem cell researcher, whose own children suffer from juvenile diabetes; he has previously done pioneering research on how beta cells grow during development.

In the study, the team reports that young mice given the hormone grew just enough new beta cells to counteract the drug's effects, no more.

"Before it can be established if this finding has any relevance to human therapy it will need to be established (that) the molecule drives beta cell replication in humans," says beta cell expert Peter Butler of the University of California, Los Angeles, by e-mail. He cautions that "a variety" of compounds have earlier been identified that drive beta cell growth in young mice but these have then not had the same effect on beta cells in people.

The study researchers acknowledge they don't know exactly how the hormone spurs the growth of beta cells, whether directly or by triggering a cascade of activity that leads to more of them. The researchers have entered into agreement with two pharmaceutical firms, Evatec and Jansen, to investigate treatments with the hormone. The study was largely funded by research money from the 2009 federal stimulus, Melton says.

Despite his enthusiasm, Kushner also cautioned that if the hormone proves less effective in older mice, that would limit its appeal for use in adult-onset diabetics, who usually develop the disease in their 50s. And if the hormone grows beta cells by causing existing ones to divide and grow directly, it might be less useful for juvenile diabetes, where beta cells have largely been wiped out. "It is a nice example of basic researchers working with pharmaceutical research, a drug that causes insulin resistance, to uncover something fundamental to biology that might help people," he says.