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Harvard: Betatrophin Hormone Found to Increase Production of Beta Cells in Mice Thirty Fold

Jul 4, 2013

The hormone, called betatrophin, caused up to a 30-fold boost in the production of beta cells….

Researchers at Harvard University’s Stem Cell Institute, led by the institute’s co-director Douglas Melton, have found a hormone that increases the ability of miceto produce their own natural insulin.

The hormone, called betatrophin, caused up to a 30-fold boost in the production of beta cells, the cells in the pancreas that make insulin.

"Imagine instead of taking three insulin injections a day, if you took one injection of betatrophin a month, or every year," said Melton, then, "your body makes more beta cells and then those beta cells produce the insulin you need."

And unlike synthetic insulin injections and pumps, beta cells only produce insulin when it’s needed, promising the potential for much greater natural control of blood sugar, and reduced complications associated with poor management of the disease.

Unlike red blood cells, which are continuously produced throughout life by stem cells in the bone marrow, beta cells reproduce through replication, or self-copying,meaning that once all existing cells are gone, there can be no more.

While Melton believes betatrophin may be able to help slow the progression of type 1, he said it is more likely to help those with type 2 diabetes, who account for about 90 percent of diabetes cases.

It’s unclear in these patients if the beta cells are still producing adequate insulin but the body cannot use it; if the cells are overtaxed by the excess demand and stop working; or if there is a gene defect that prevents the body from making adequate beta cells to keep up with the demand, Melton said.

"It takes a diabetic person years to kill off their beta cells," he said. "I think therefore if we provide a new [dose] of them, it will again take years for them to wear out. It won’t be a permanent cure, but if you can do this three times in your life and each time it lasts for 10 years, then that will probably be enough."

Melton said his lab, which is "sort of obsessed" with beta cells, discovered betatrophin in the fat and liver of diabetic mice that had been given a medication to block their bodies from using insulin. In response, a gene that no one had studied before kicked into high gear and the mice ramped up their beta-cell production.

The team isolated the gene (which they initially dubbed, tongue in cheek, "mo’beta") and found that not only did it rev up beta-cell production in mice, but it also exists in people.

"This gene is expressed in people in the same way," Melton said. "Betatrophin is in the liver, and it’s in the serum. Now what we have to do is prove that if you inject the protein into a human, it will do the same thing."

But first, and perhaps more importantly, they need to figure out if an injection of betatrophin actually cures diabetes in a more realistic model of the disease. The mice that Melton and his team used initially were genetically altered to mimic the disease, but are very different from the real thing.

"It’s sort of like a circus trick," he said, referring to the technique researchers use to creatediabetes symptoms in mice that aren’t diabetic. To really see if betatrophin works, they have started a test on obese mice that have become diabetic after being raised on high-fat diets.

"If we can’t improve the health of a rodent by giving it more beta cells, then it means that we don’t understand what’s going on," Melton said.

Those results could be available in the fall.
Cell, May 2013