'Breakthrough' Diabetes Article Retracted

Miriam E Tucker

December 29, 2016

An article reporting what had been hailed as a possible "breakthrough" in the search for a biological cure for type 1 diabetes has now been retracted.

The article, "Betatrophin: A hormone that controls pancreatic β-cell proliferation," received a great deal of attention in the diabetes community and in the media when it was published in the journal Cell in May 2013. The authors, Peng Yi, PhD, Ji-Sun Park, and Douglas A Melton, PhD, of Harvard University, Cambridge, Massachusetts, had suggested that this newly identified hormone ― also called Angptl-8 ― could potentially expand beta-cell mass and thereby boost endogenous insulin secretion in diabetes patients.

However, subsequent research from another group failed to replicate the findings. All studies were in rodents. In response, Dr Yi and colleagues published an open-access correspondence in the same October 2014 issue of Cell in which they reported that they too had conducted subsequent experiments that did not replicate their earlier findings. They postulated reasons for the differences.

Now, they have voluntarily retracted the original article. "We have subsequently repeated a series of blinded experiments with [another] lab and have now determined conclusively that our conclusion that Angptl-8/betatrophin causes specific β-cell replication is wrong and cannot be supported. Therefore, the most appropriate course of action is to retract the paper. We regret and apologize for this mistake."

Asked to comment, Mark A Atkinson, PhD, director of the University of Florida Diabetes Institute, in Gainesville, told Medscape Medical News, "Actually, I see this as an event that should, in the end, be extremely beneficial for medical research and type 1 diabetes in particular. Recently, questions have abounded in the medical literature regarding reproducibility of data and its effects on medical advances. I believe Dr Melton's experience, while on the surface clearly disappointing, serves as an important model for every researcher seeking to find the truth."

In their prior correspondence, the authors noted that although other laboratories had reproduced parts of their betatrophin results, altogether the data "show a significant and unsatisfactory variation, perhaps as a result of liver inflammation, which makes it difficult to draw a secure conclusion about beta-cell replication."

They also note that "the agents responsible for inducing beta-cell replication...may be triglyceride levels, members of the Angptl family, or some other factor(s) yet to be identified. We are committed to solving this puzzle in mice and then move on to determine whether or not any of these findings in mice are relevant to the human condition."

Dr Atkinson said, "There is so much positive development going on within the cell-therapy field. As for molecules capable of inducing beta-cell replication, while betatrophin may have seen its day, there is a small handful of other molecules having similar properties that are undergoing testing. I believe that field will also move forward without much impact."

He also praised the lead author, Dr Melton, as a "renowned world-class cell biologist" whose prior work had been replicated. "If everyone participated in cooperative efforts seeking validation of important discoveries as he did, scientists, companies, and the general public would benefit through more efficient advances in health care products."

For the original work, Dr Ye was supported by a fellowship from the Helen Hay Whitney Foundation. The work was supported by grants from the National Institutes of Health and the Harvard Stem Cell Institute. At the time, Dr Ye and Dr Melton were listed as inventors on a US patent application based on this work and were pursuing further studies with two pharmaceutical companies. Dr Atkinson has disclosed no relevant financial relationships.

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Cell. Published online December 27, 2016. Retraction



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