Diabetes mellitus now affects more people than ever, with nearly one in ten Americans suffering from it, and the number of diabetics in developing countries is growing rapidly. And while treatments are constantly improving as research progresses, the currently available therapeutic options are far from ideal. But a major breakthrough in diabetes research recently reported by a group of scientists in the journal Cell Phone offers a new hope for radically new and improved ways to combat this disease.
The research team at Harvard led by Douglas Melton focused on the pancreatic beta cells that are responsible for the production of insulin. In type I diabetes, these cells are gradually destroyed by the body’s immune system, and in type II diabetes, but at some point begin to fail as the disease progresses, making them a prime target for possible new therapeutic approaches for diabetes. In healthy people, beta cells usually divide at a rather sluggish rate, with the total remaining more or less constant. But it has been known for some time that under certain conditions, such as pregnancy, they can multiply much faster. The aim of the scientists was what exactly triggers this proliferation, and whether this will then be used to increase their numbers for therapeutic purposes.
Working with mice as model animals, she first devised a way to replicate her body’s perception as if insulin lacked what they hoped would replicate the beta cells faster. They did this by using an injection of insulin receptor antagonists, which prevents the insulin binding to its receptors in different tissues, effectively blocking its action. The effect of this blockade turned out exactly as they had hoped: when mice were given the insulin antagonist, their beta cells responded rapidly by dividing faster and more numerous.
Once the beta cells were awakened in division faster, the scientists were able to investigate what mechanism lay behind this effect. First, they quickly ruled out the possibility that the insulin antagonist acted directly on the beta cells. This could then only mean that another substance released to other tissues and acting on the beta cells in the pancreas – a description incorporating a hormone – had to be responsible. How many hormones are peptides and thus encoded by specific genes, then researchers decided how the administration of insulin antagonists affects gene expression in different tissues. In particular, a gene caught their attention because its expression in liver cells greatly increased in response to insulin receptor blockade. Furthermore, this gene had some properties that it encodes for a peptide secreted from the cells, as suggested for a hormone. They called the gene and its product betatrophin, which comes from the Greek and translates into about ‘beta nutritious.’ Importantly, humans also possess a betatrophin gene and the hormone is also produced in the human liver.
The last step was to show that they really found the right substance. Instead of trying to isolate betatrophin or somehow produce and inject it into the mice, additional copies of the gene are inserted betatrophin them into the liver cells, thereby significantly increasing the production of the hormone. The beta-cell response was fast and vigorous: once betatrophin production started in the liver, its proliferation rate increased by more than 30-fold! As a result, the pancreas of the mice was elevated in betatrophin able to produce larger amounts of insulin, to the point that glucose tolerance was even better than that of healthy mice.
Extrapolating these results to humans, it is not difficult to imagine what this means for diabetics. Injecting betatrophin once a week, for example, would increase the proliferation of their ailing beta cells, increasing insulin production and ensuring natural glycemic control – which is far better than having to rely on insulin injections.
Of course, it is far too early to celebrate a new revolution in diabetes therapy. It remains to be seen if the results in mice are also reproduced in humans; It has happened before that results that very promising mice could be replicated in human clinical trials are being sought. We thus have to wait for further studies, and until scientists are able to produce enough to try it in betatrophin humans, we can not be sure what to really expect.
But the discovery of a new hormone that can increase the proliferation of insulin-producing cells is still exciting news. Because even if the further research ultimately proves disappointing, or shows that the real story behind betatrophin is more complicated than it looks now, there will still be radically new leadership in the search for better treatments for diabetes – and with it the hope for a healthier and longer life for the billions of diabetics worldwide.