I finally got a chance to read the Cell paper by the Melton team on Betatrophin and it is quite cool. Update — Unfortunately the Betatrophin paper discussed here originally back in 2013 has now largely been proven to have come to incorrect conclusions (for more read this).
I think one big question is whether this can this be translated into humans, but it seems very encouraging.
Another question is whether Betatrophin or some derivative when given as a chemical pill to patients could help control blood sugar. In other words, do we have a drug here? I hope so!
A final big question is the mechanism by which Betatrophin works as the authors conclude in the paper:
We do not yet know the mechanism of action for betatrophin. It may act directly or indirectly on b cells to control their proliferation. Identification of the betatrophin receptor and/or other possible cofactors will help to explain how the liver and fat interact with the pancreas to regulate b cell mass. Nonetheless, identification of betatrophin as a hormone that can exert control on b cell replication and b cell mass opens a new door to possible diabetes therapy.
Above Melton and his postdoc Peng Yi (see image at the top) discuss the discovery and give us a behind the scenes look at what went into in the video above.
How often do we get a window into the world of a big scientific discovery like this video? Very intriguing!
I’ve been in science long enough to remember the tremendous excitement at the initial discovery of leptin. It was hyped as a possible cure for obesity, but turned out that human obesity is much more complex than ob/ob mice. I’m really curious how betatropin story folds out in human.
I have been in science long enough that when erythropoietin was first purified, I was a graduate student in that lab. It went on to be a blockbuster for treating people anemia due to kidney failure (not to mention one of the most abused drugs in sports).
It’s hard to say the clinical application. Betatrophin is also named TD26, a hepatocellular carcinoma-associated protein. That means it also highly expresses in some kinds of cancer, but those patients with such cancer would have more beta cells? That would be interesting to determine the correlation between the beta cell mass and the TD26 expression level under different physiological and pathological status, even the expression level of the receptor(s) which is still pending to be identified in beta cells..
To be honest, this paper is just the very very beginning step to claim a promising and potent drug/target to treat diabetes. 1) the next should be examining how the action is for human beta cells using primary islets. Actually it’s strange why the authors didn’t provide any data at all, given that they have already made the overexpression vector and the recombinant protein TD26 is also commercial available. 2) genetic model will diminish the challenge on the technique in terms of hydrodynamic tail
vein injection. 3) mechanism, particularly the receptor/target in beta cells, will be necessary to evaluate the future clinical application.
Everything looks promising. Just wish betatrophin is not the next leptin.