More Beta Cells, More Insulin, Less Diabetes
Posted on by Dr. Francis Collins
Caption: Betatrophin, a natural hormone produced in liver and fat cells, triggers the insulin-producing beta cells in the pancreas to replicate
Credit: Douglas Melton and Peng Yi
Type 2 diabetes (T2D) has arguably reached epidemic levels in this country; between 22 and 24 million people suffer from the disease. But now there’s an exciting new development: scientists at the Harvard Stem Cell Institute have discovered a hormone that might slow or stop the progression of diabetes [1].
T2D is the most common type of diabetes, accounting for about 95% of cases. The hallmark is high blood sugar. It is linked to obesity, which increases the body’s demand for more and more insulin. T2D develops when specific insulin-producing cells in the pancreas, called beta cells, become exhausted and can’t keep up with the increased demand. With insufficient insulin, blood glucose levels rise. Over time, these high levels of glucose can lead to heart disease, stroke, blindness, kidney disease, nerve damage, and even amputations. T2D can be helped by weight loss and exercise, but often oral medication or insulin shots are ultimately needed.
Treating diabetes costs the U.S. a veritable fortune. Last year the bill came to $245 billion [2]—that’s $176 billion in direct medical costs and another $69 billion in lower productivity. We need a game changer. The new discovery just might lead to that, though it won’t happen overnight.
The NIH-funded researchers set out to try to identify a signal that seems to be sent by the liver to the beta cells when the insulin receptor is blocked and blood glucose levels rise. The researchers found that after the insulin receptor was blocked, one particular liver gene increased its activity rather dramatically. They were able to show that this gene, which turned out to be one of the 20,000 genes that hasn’t attracted much attention so far, coded for a secreted protein. Because it helps beta cells grow, they named it “betatrophin.” This work was done in the mouse, but there’s an almost identical counterpart in the human. When the researchers engineered normal healthy mice to manufacture more of the hormone in their livers, the pancreas responded and made more insulin-producing beta cells.
Betatrophin sends the beta cells into a frenzy causing them to replicate as much as 30 times their normal rate! No other chemical or natural protein has ever caused such a dramatic boost in beta cell proliferation.
It’s not every day that a new and important hormone is discovered! But betatrophin has an important normal role in maintaining normal glucose levels. The amount of betatrophin produced in the liver (and in fat cells) rises naturally whenever the body needs to expand its inventory of beta cells: for example, during pregnancy, when the mother’s body needs to make more beta cells to accommodate the demands of the fetus.
The next step will be to see whether these extra beta cells, produced by administration of betatrophin, can produce enough insulin to halt and possibly reverse the disease in sick diabetic mice. If all goes well, we could be testing betatrophin in humans within two or three years.
Betatrophin could also help treat type 1 diabetes, which develops because the immune system attacks and destroys the insulin-producing beta cells in the pancreas. Currently, the only treatment for type 1 diabetes is insulin shots. But the researchers suspect that betatrophin might work during a critical time called the “honeymoon” period, which is a short window after the onset of disease but before all the patients’ beta cells have been wiped out.
In the future, rather than taking three insulin shots every day to treat their disease, people with T2D might receive a weekly or monthly betatrophin injection to produce more beta cells and keep their blood sugar at a healthy level. That would be a true paradigm shift in the treatment of this disease.
References:
[1] Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation. Yi P, Park JS, Melton DA. Cell. 2013 Apr 24
[2] Economic Costs of Diabetes in the U.S. in 2012. American Diabetes Association. Diabetes Care. 2013 Apr;36(4):1033-46.
Links:
National Diabetes Information Clearinghouse (NDIC): NIDDK
National Diabetes Statistics 2011: NDIC/NIDDK
NIH support: The National Institute of Diabetes and Digestive and Kidney Diseases
Fascinating work! It will be interesting to see how it pans out. There has been significant progress recently with the development of the Glucagon-like peptide 1 receptor agonists, which is a good example of how venom research is aiding the development of novel therapeutics.
I think diabetes is due to bacterial infection. Otherwise, how it is possible to spread worldwide? If we go find that bacteria, then it will be helpful to the whole world. … What do you think?
I suspect the same. Could high blood sugar levels also be caused by stress?
This is really great! Could betatrophin be at all useful in work on regenerating beta cell colonies for type 1 diabetics? I am not sure how feasible this is, but by using progenitor cells to build functioning beta cells in the islets, could their restoration be amplified using betatrophin? Or will restoring a type 1 diabetic to full health require a much more careful balance of the number of beta cells, such that amplifying this with betatrophin may lead to increased rates of hypoglycemia?
Also, Sitansu: I doubt it. There are many ways to explain the worldwide spread of T2D, including many far more everyday causes (lifestyle changes, nutrition, etc.). See http://care.diabetesjournals.org/content/34/6/1249.full
Could diabetes sometimes be caused by stress or bacteria without genetic predisposition?
Does obesity lead inevitably to diabetes?
Type 2 DM has insulin resistance as its main cause, so I wonder if betatrophin will be so effective.
Shall we discuss about the general standard for a mammalian hormone like betatrophin?
As everything in life, money is key for making this go through development, clinical trials, FDA and production. I know the cancer drugs are now being developed on a much faster track than years ago. Given the fact that there are so many type 2 diabetics around the world, and particularly in the US (22 Million, I hear) this should be enough incentive for fast tracking this project.
I wonder if anyone knows more about the development schedule for this hormone.
This is a major discovery. For years no one has provided the mechanism for how insulin resistance triggers hyperinsulinemia. How does the liver or peripheral cells communicate with the beta cells? Why is it that one individual can compensate for obesity induced insulin resistance by mustering up a robust insulin response and maintain euglycemia whereas another individual cannot and destined to become diabetic. It will be intriguing to measure the levels of beta- tropin in insulin resistant folks with and without diabetes as well as in pregnancy, PCOS, lipodystrophy,etc.
Where are the cures promised 10-15 years ago for diabetes? Nowhere. Where will the cures promised today be 10-15 years from now? Nowhere. Hormones like betatrophin and companies … that have a product that can cure type 1 and 2 diabetes should be doing so now, if not in the USA then some other country.
There are always risks in medical treatments and there is no perfect treatment or drug, but you use the best you got today and add improvements with time. Medical clinical trials that take decades are really in the dark ages. We the people are willing to take risks. Far more people are going to die from lack of treatment then the treatment. Please, enough mice and rats have been cured. Is it not time to cure humans?
Fascinating article. The theory seems good and it will be interesting to see where this will go. Considering the millions that have type 2 diabetes, this would truly be great for them. If this were to work, I, of course, wonder about the long-term implications of a betatrophin injection.