Potential Diabetes Breakthrough

 Diabetes Breakthough  

A newly discovered hormone in mice prompts the rodents to boost their production of pancreatic β cells, the ones that make insulin and are missing or not productive enough in patients with diabetes. The hormone, called betatrophin, is made by people as well, and its discoverers hope that the effect in the human pancreas might be similar.

Researchers at the Harvard Stem Cell Institute (HSCI) have discovered a hormone that holds promise for a dramatically more effective treatment of type 2 diabetes, a metabolic illness afflicting an estimated 26 million Americans. The researchers believe that the hormone might also have a role in treating type 1, or juvenile, diabetes.

The work was published today by the journal Cell as an early online release. It is scheduled for the May 9 print edition of the journal.

The hormone, called betatrophin, causes mice to produce insulin-secreting pancreatic beta cells at up to 30 times the normal rate. The new beta cells only produce insulin when called for by the body, offering the potential for the natural regulation of insulin and a great reduction in the complications associated with diabetes, the leading medical cause of amputations and non-genetic loss of vision.

In the image above from researcher Peng Yi, a mouse pancreas is sectioned and the hormone betatrophin prompts insulin-producing β cells (green) to replicate (new cells are red).

The researchers who discovered betatrophin, HSCI co-director Douglas Melton and postdoctoral fellow Yi, caution that much work remains to be done before it could be used as a treatment in humans. But the results of their work, which was supported in large part by a federal research grant, already have attracted the attention of drug manufacturers.

“If this could be used in people,” said Melton, Harvard’s Xander University Professor and co-chair of the University’s Department of Stem Cell and Regenerative Biology, “it could eventually mean 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, or in the best case maybe even once a year.”

Type 2 diabetes, a disease associated with the national obesity epidemic, is usually caused by a combination of excess weight and lack of exercise. It causes patients to slowly lose beta cells and the ability to produce adequate insulin. One recent study has estimated that diabetes treatment and complications cost the United States $218 billion annually, or about 10 percent of the nation’s entire health bill.

“Our idea here is relatively simple,” Melton said. “We would provide this hormone, the type 2 diabetic will make more of their own insulin-producing cells, and this will slow down, if not stop, the progression of their diabetes. I’ve never seen any treatment that causes such an enormous leap in beta cell replication.”

Though Melton sees betatrophin primarily as a treatment for type 2 diabetes, he believes it might play a role in the treatment of type 1 diabetes as well, perhaps boosting the number of beta cells and slowing the progression of that autoimmune disease when it’s first diagnosed.

“We’ve done the work in mice,” Melton said, “but of course we’re not interested in curing mice of diabetes, and we now know the gene is a human gene. We’ve cloned the human gene and, moreover, we know that the hormone exists in human plasma; betatrophin definitely exists in humans.”

Image Source: Cell

While Melton was clear about the need for more research before the hormone could be available as a drug, he also said that betatrophin could be in human clinical trials within three to five years, an extremely short time in the normal course of drug discovery and development.

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As is often the case in basic science research, serendipity played a role in the discovery of betatrophin, which Melton and Yi originally called Rabbit because they discovered it during the Chinese Year of the Rabbit, and because it makes beta cells multiply so quickly.

For more than 15 years the major focus of Melton’s work has been not type 2 diabetes but the less common type 1, or juvenile diabetes, which he began focusing on when his son was diagnosed with it as an infant.

Additionally, most of Melton’s work has involved using stem cells, the fundamental building blocks of all human organs, as disease treatments and targets for drug discoveries. But stem cells played no direct role in the discovery of betatrophin. It was, rather, a classic example of scientists with sufficient resources asking questions, and pursuing answers, that fell outside the usual scope of their laboratories and institutes.

“I would like to tell you this discovery came from deep thinking and we knew we would find this, but it was more a bit of luck,” explained Melton, who in addition to his roles at Harvard is a Howard Hughes Medical Institute investigator. “We were just wondering what happens when an animal doesn’t have enough insulin. We were lucky to find this new gene that had largely gone unnoticed before.




SOURCE  Harvard Gazette

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