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Harvard Cell Growth Discovery Seen Treating Diabetes

Harvard University scientists discovered a hormone that spurs the growth of beta cells, the body’s insulin factories, a finding that holds promise for treating diabetes in a new way.

Researchers first found the hormone, called betatrophin, in mice, where it increases beta cell growth by as much as 33 times, said Douglas Melton, co-director of the Department of Stem Cell and Regenerative Biology at Harvard in Cambridge, Massachusetts. An almost-identical hormone in humans appears to serve the same function, Melton and his colleagues said today in the journal Cell.

The discovery has drawn the interest of drugmakers looking at the $42 billion market for diabetes medicines. Harvard has applied for a patent on betatrophin, and the molecule has been licensed to Hamburg, Germany-based Evotec AG and Johnson & Johnson, Melton said. New drugs are needed as patients develop resistance to older therapies.

“We’re very excited about this,” Melton said in a telephone interview. “The finding just makes so much sense to me, and it could be a new way forward in treating diabetes.”

About 347 million people, or 5 percent of the world’s population, have diabetes, a condition that can lead to heart disease, stroke, eye disease and nerve damage, according to the World Health Organization. Many patients develop these conditions even while getting treatment, so new drugs are needed, Melton said.

Blood Sugar

Diabetes occurs when the body fails to regulate levels of sugar in the blood that cells need for nourishment. Most diabetes patients have the Type 2 form, which occurs when the body loses its response to insulin, the hormone that regulates blood sugar.

Patients develop Type 1 diabetes when damage to beta cells depletes insulin levels. Melton, who has two children with Type 1 diabetes, has been trying use stem cells to replace the beta cells damaged or lost in the disease.

Compared with other tissues, beta cells normally grow very slowly, and only about 1 in 1,000 to 1 in 10,000 beta cells divides daily, Melton said. Using a chemical blocker, Melton and his colleagues Peng Yi, a postdoctoral fellow in the lab, and Ji-Sun Park, a laboratory technician, fooled the mice’s bodies into thinking they had completely stopped making insulin. That led to an increase in beta cell production, he said.

The researchers turned their attention to finding out what caused the increase. Melton and his colleagues found a gene that becomes more active in liver and fat cells when insulin levels drop. When applied directly to mouse beta cells, the protein made by this gene increased the rate of growth.

Pregnant Mice

Further studies showed that betatrophin levels rise in pregnant mice, which are known to have increased beta cell growth rates to make insulin for the gestating animals in the womb. The gene that makes betatrophin is also highly active in mice bred to develop diabetes.

Studies of the human form of betatrophin and its effects are just beginning, Melton said. He noted that betatrophin appears to improve blood sugar control in mice that received the hormone.

“This is going to get a lot of attention and a lot of study,” said Gordon Weir, a Harvard Medical School professor of medicine at the Joslin Diabetes Center in Boston. “The next question is whether this acts directly on beta cells in humans.”

Some diabetes drugs, called sulfonylureas, that increase the amount of insulin made by beta cells tend to lose their impact in patients after a few years as beta cells lose their strength. In addition, the body’s response to insulin drops, a phenomenon called insulin resistance. Betatrophin may present an alternative that would both add to beta cells numbers and fight insulin resistance, Melton said.

Type 1

Betatrophin might also be useful when patients develop type 1 diabetes, the form of the disease in which the body’s immune system mistakenly destroys beta cells, he said. Giving the hormone might help the body counteract this autoimmune attack, he said.

Anything that stimulates the replication of beta cells would have tremendous implications for treatment, said John Anderson, president of medicine & science for the American Diabetes Association, an advocacy group based in Alexandria, Virginia. While the discovery improves understanding of beta cell replication, many questions must be answered before it could be used as a drug, he said.

“Does it work in humans and does it work for a long time in humans?” he said. “Does it suffer from the same kind of burnout that other medications suffer from?”

Johnson & Johnson, the world’s largest seller of health-care products, is based in New Brunswick, New Jersey. The company won U.S. market clearance for canagliflozin, a treatment for diabetes, in March.

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