Biologists have found a hormone in the liver that spurs the growth of insulin-secreting cells in the pancreas, a discovery they hope will lead to new treatments for diabetes.
A team led by Douglas Melton, co-director of the Harvard Stem Cell Institute in Cambridge, Massachusetts, identified the hormone, betatrophin, also found in the human liver, that caused in animals, insulin-secreting pancreatic ß cells to proliferate. Further experiments showed that 8-week-old mice injected with betatrophin showed an average 17-fold rise in the replication of their insulin-secreting pancreatic ß cells, the researchers report in Cell. “It’s rare that one discovers a new hormone, and this one is interesting because it’s so specific,” says Melton. “It works only on ß cells and it’s so robust and so potent.” 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,
Pancreatic ß cells replicate rapidly during embryonic and neonatal stages in both mice and humans, but their growth falls off dramatically in adults. A decrease in the function of the cells late in life is the main cause of type 2 diabetes, a metabolic disorder that affects more than 300 million people worldwide. 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.
He also hopes that betatrophin will be able to help people with type 1 diabetes. Matthias Hebrok, director of the University of California, San Francisco, Diabetes Center, says that the work “is a great advance”. “The findings are very interesting,” he says, although he would like to see the experiments repeated in older mice. Henrik Semb, managing director of the Danish Stem Cell Center in Copenhagen, says that "the identification of a factor, betatrophin, that stimulates mouse ß-cell replication with remarkable efficiency is a very important discovery, because it provides the starting point for further studies to elucidate the underlying mechanism of ß-cell replication."
How did this discovery come about?
A hint came from studying something that people know about but don’t think much about, which is: What happens during pregnancy?” he said, “When a woman gets pregnant, her carbohydrate load, her call for insulin, can increase an enormous amount because of the weight and nutrition needs of the fetus. Melton and his group have been working on the project for more than four years. During pregnancy, there are more beta cells needed, and it turns out that this hormone goes up during pregnancy. We looked in pregnant mice and found that when the animal becomes pregnant this hormone is turned on to make more beta cells.”
“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.”
The work was published by the journal Cell as an early online release. It was scheduled for the May 9 print edition of the journal.
The researchers who discovered betatrophin look at it primarily as a treatment for type 2 diabetes, caution that much work remains to be done before it could be used as a treatment in humans. Melton thinks that injections of betatrophin once a month, or perhaps even once a year, could induce enough activity in pancreatic ß cells to provide the same level of blood-sugar regulation for people with type 2 diabetes as daily insulin injections do. But more importantly, he adds, they would cause fewer complications because the body would be making its own insulin.
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.
Producing enough betatrophin for testing in human clinical trials will take about two years, according to Melton, who is also working to identify the hormone’s receptor and its mechanism of action .
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 two years, an extremely short time in the normal course of drug discovery and development.