Diabetes Breakthrough: Newly Discovered Hormone Betatrophin Could Eliminate Insulin Injections

Daily insulin injections are the routine for many people with type 2 diabetes. But they might be able to break free from that regimen if a newly discovered hormone realizes its promise.

So far, the hormone betatrophin has been examined only in mice, so there’s still much work to do before it can even be tested in humans. But hopes are high -- the researchers have already cloned the human gene for betatrophin, and they know it exists in human plasma -- that it could be used to increase the number of insulin-producing cells in the pancreas.

"If this could be used in people, 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," Harvard researcher Doug Melton said in a statement Thursday.

Type 2 diabetes, estimated to affect about 26 million people in the U.S. alone, is often linked to obesity. People with this condition either do not produce enough insulin to regulate their blood sugar effectively or they have some resistance to insulin’s effects. This kind of diabetes used to be primarily found in adults, but it has begun cropping up more in children as the rate of childhood obesity rises.

The research sprang from the Harvard Stem Cell Institute, of which Melton is co-director, but oddly enough stem cells actually didn’t play a role in the discovery. A paper describing the work was published online Thursday in the journal Cell. Melton and coauthor Peng Yi have already have signed a collaborative agreement with German biotechnology firm Evotec and licensed a betatrophin compound to a Johnson & Johnson subsidiary called Janssen Pharmaceuticals.

According to Melton, finding the right hormone was a stroke of luck -- they were investigating what happens when animals don’t make enough insulin. Thanks to previous research, they knew that, when the insulin pathway is blocked in the liver, there’s some process that induces the pancreas to make more insulin-secreting beta-cells in response.

So Melton and Yi treated mice with a small protein called S961, which blocks insulin signaling and induces glucose intolerance. Sure enough, the mice started making more beta-cells. The researchers tried adding S961 directly to mouse beta-cells in the lab, but there was no observed effect. Therefore, they realized there had to be some intermediary in the process that eventually signals the pancreas to start making more beta-cells.

Using what’s called a DNA microarray analysis, the researchers looked at the expression levels of various genes in mouse tissues known to be involved in regulating the metabolism -- liver tissue, white fat and skeletal muscles -- after S961 treatment. They soon zeroed in on a single gene, which they called betatrophin, which encodes for a protein that is 198 amino acids long. After S961 is applied, the level of betatrophin expression jumps in both the liver and white fat tissues.

When Melton and his colleagues induced the livers of living mice to make more betatrophin, there was “a striking increase in beta-cell replication,” an average of 17-fold higher than in control animals, the scientists wrote.

There are still some questions to be answered -- primarily, figuring out how betatrophin acts on pancreatic beta-cells. But the finding definitely opens the door to a possible therapy for type 2 diabetes and possibly leads to treatments for type 1 diabetes, also called childhood diabetes.

“Our idea here is relatively simple,” Melton said Thursday. “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.”

SOURCE: Yi et al. “Betatrophin: A Hormone that Controls Pancreatic Beta-Cell Proliferation.” Cell published online 25 April 2013.