Betatrophin: The Finding That Eliminates Diabetes or Just Another Alluring Promise?

Betatrophin: The Finding That Eliminates Diabetes or Just Another Alluring Promise?

A recent article in the journal Cell sent shock waves through the diabetic community as a new finding offered to restore the beta cells lost through the ravages of the diabetic process. Will diabetes be overcome or is this just another provocative promise?

The article revealed a newly identified hormone called betatrophin. This is a naturally occurring hormone that could be used by injection to overcome type 2 diabetes mellitus (T2DM) and possibly type 1. Research in this area came from the Harvard Stem Cell Institute, and ironically didn’t involve stem cells. In a quite unexpected fashion, researchers detected that betatrophin caused regeneration of previously lost beta cells and restoration of more robust insulin secretion, significant enough to resolve previously established diabetes.

This whole idea is certainly plausible. Several years ago, a researcher named Butler published results on the postmortem pancreatic mass of various individuals. Of course, these were autopsy studies of people who had died of non-pancreatic causes. He found that non-diabetic obese subjects had a pancreatic beta cell mass expanded beyond that of thin individuals. This suggests that through some means, beta cell mass can be expanded to meet increased need. And his study showed that as pre-diabetes and diabetes set in, the beta cell mass shrank noticeably. 

These findings touched off quite a debate about whether it is beta cell mass or beta cell “capacity” that governs the ultimate production of insulin in response to glucose demand (lots of beta cells producing some insulin or some beta cells producing a lot of insulin). The betatrophin researchers have found that this hormone does seem to expand the beta cell mass and aids in overcoming T2DM by expanding insulin production.

Interest in the idea of expanding beta cell mass first was raised by animal studies with GLP-1 receptor activators (GLP-1 RAs). Data on humans in this regard has been predictably limited (humans don’t readily acquiesce to pancreatic biopsy). At least in rats, GLP-1 RAs seem to expand beta cell mass! However, a couple of years ago at the annual American Diabetes Association (ADA) meeting, Dr Dave D’Alessio presented data showing that this doesn’t occur in all rats, just the very young ones. And while we know that GLP-1 RAs enhance beta cell function in humans while the patient is receiving the drug, there is no clear evidence to suggest this effect is carried over (as one would expect with an expanded beta cell mass) if the drug is stopped.

So, is betatrophin an interesting “parlor trick” that can be performed in lab rats or a real breakthrough in diabetes prevention and control that is applicable to humans? 

At this point, the answer is “We can’t yet know.” Obviously, the appeal of a weekly or monthly injection that will expand beta cell mass and overcome diabetes is enormous! From our recent experience with GLP-1 RAs, we know the path to realization of this dream is strewn with potholes, rubble, hills, and gullies. 

Dr Robert Ratner, chief scientific officer of the ADA, recently announced that the annual cost of care for diabetes in the US in 2012 was $247 billion—more than the estimates projected for 2020! We cannot continue on the current path of coping with an expanding population of patients with T2DM and its complications without facing financial destruction. Any new discovery that can alter the natural history of diabetes, or stop it altogether, is of enormous importance. 

Time will tell if betatrophin is a step toward eradicating diabetes or just another interesting finding in lab animals. For now, I wish the researchers at Harvard “fair winds and following seas” as they sail into this new area of inquiry.


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