Will Betatrophin Cure Type 2 Diabetes?

Patient Expert

What if our beta cells, the cells in the pancreas that produce insulin, could be instructed to multiply so they could produce more insulin when we needed it? That's what happens when women are pregnant and need more insulin because of their increased weight.

Harvard scientists think they may have discovered how to get this to happen. They've discovered a hormone, which they call betatrophin, that seems to produce beta cells at up to 30 times the normal rate. Although, like insulin, the hormone would have to be taken by injection, the injections would be much less frequent than standard insulin injections, maybe once a week, once a month, or even once a year, according to the researchers, because it's stimulating an increase in beta cell mass.

The research was done in mice, and we all know that mice have been cured of diabetes hundreds of times. As Doug Melton, codirector of Harvard's Stem Cell Institute and one of the researchers involved with this study said, "Of course, we're not interested in curing mice." But they've shown that humans have a betatrophin gene, which Melton says is almost identical to the mouse gene, and the hormone betatrophin is present in human plasma. They don't yet know if pregnant women produce more betatrophin, but they're looking into that possibility.

Although the idea is aimed primarily at type 2 diabetes, it might also help with type 1 diabetes. The problem in the latter disease is that the body's own immune system is attacking the beta cells, so even when they multiply, they're inactivated by the autoimmune response. So giving someone in the early stages of type 1 diabetes the hormone would have to be accompanied with giving them an immune-suppressing drug.

One problem with anything that makes cells multiply faster is that multiplying faster is what cancer cells do. Could betatrophin induce signals that caused beta cells to multiply and keep multiplying even without the new hormone? That doesn't happen in pregnancy. After the baby is born, the increased beta cell mass begins to regress and reverts to its prepregancy size. But another name for the betatrophin protein is TD26, a hepatocellular carcinoma-associated protein.

Presumably the oft-suggested "further study" would address this problem. Melton estimates that human trials of betatrophin won't begin for three to five years.

Another problem is that people with type 2 often produce more insulin than normal but can't use it effectively because of insulin resistance. The best cure for type 2 is to reduce insulin resistance rather than producing more insulin (as occurs with the sulfonylurea drugs) or injecting it. However, the sulfonylurea drugs make the beta cells produce more insulin even in the absence of high glucose levels, and this can cause hypoglycemia (low blood sugar). Injected insulin can do the same.

So it would be better to have more beta cells that only produced insulin when you needed it. Another advantage of insulin you produce yourself is that it goes right to the liver, which removes a lot of it, so insulin levels in the liver are high and stop the liver from pouring out glucose, but not in the periphery. Injected insulin results in high insulin levels in the periphery and lower levels in the liver, which doesn't match normal physiology.

However, people with type 2 diabetes usually have not only insulin resistance but also leptin resistance as well as resistance to one of the incretin hormones, GIP. Will it turn out that they have betatrophin resistance too?

Hence there are many unanswered questions about this new hormone. It may turn out to be the most exciting discovery since the isolation of insulin. Or it may turn out not to fulfill its promise, as happened with leptin, which was supposed to be the answer to obesity.

But I think this research is a good example of how a lot of medical research occurs. Academic researchers, usually supported by federal research grants, do the basic research. They're not specifically looking for drugs. They're trying to figure out how things work.

Once you know how things work, then you can try to find a drug that will affect that process, and the drug development is usually undertaken by the drug companies, who have the money to fund the huge clinical trials that are needed to get FDA approval of new drugs.

In this case, the researchers are working with Evotech, a German biotech company, and Janssen Pharmaceuticals, a Johnson & Johnson company. This means that the tax dollars that initially supported the basic academic research will ultimately benefit the drug companies, as well as patients, if they can develop a drug that will stimulate the production of this hormone or produce betatrophin in amounts sufficient to be injected in many patients. Whether this is right or wrong depends on your political views.

Melton has a personal reason to want to find a cure for diabetes: his two children both have type 1. And he hasn't lost the sense of excitement that occurs when you figure something out in science. When he first saw the results that indicated that the beta cells were multiplying, he wrote to Peng Yi, a graduate student who worked on the research with him, ""Dear Peng, I can hardly sleep I am so excited by your result. It's a tribute to your hard work and hard thinking. Can't wait to see the data from the repeat. Doug."

Let's hope that budgetary constraints don't cut off the federal research funds that are so essential for good research like this. We do need Big Pharma to manufacture the drugs we need. But we need academic researchers to figure out the basics first.