Study refutes using anti-malaria drug to treat diabetes

Study refutes using anti-malaria drug to treat diabetes

A drug used to treat malaria does not, after all, create new insulin-producing cells, according to a new paper published in Cell Metabolism, refutes a study published in Cell in January.

"First we had hoped that we would be able to replicate the findings, but they didn't hold up," said the senior author. "People with Type 1 diabetes, they see these stories come out and they think maybe there's something on the horizon and then nothing ever follows through," senior author said.

The symptoms of Type 1 and Type 2 diabetes are quite similar but the underlying causes differ. In type 1 diabetes, the body fails to create enough insulin, a hormone produced by the pancreas that regulates cellular intake of nutrients. In Type 2 diabetes, cells no longer respond efficiently to insulin.

Insulin is produced in hormone-producing regions of the pancreas called islets. Within the islets are alpha and beta cells. Beta cells are integral to creating insulin.

"That's the cell that if you lose (insulin production), you get Type 1 diabetes," said the senior author. So there is always interest in any process that might generate new beta cells to replace those lost in Type 1 diabetes.

In early 2017, in a paper published in the journal Cell, a European team reported that the antimalarial drug artemether could convert alpha cells into functional beta cells. While alpha cells converting into beta cells had been described before, this was the first time an existing drug had been reported to stimulate the process and it caused a lot of excitement in the field, senior author said.

Outfitted with the precision tools to capture alpha-to-beta cellular conversion, senior author enlisted graduate student to assist with replicating the original experiment.
"We were hoping, expecting, to confirm," senior author said. "We weren't able to."

The grad student used pancreatic islets derived from mice. After around four months of experiments with artemether, it was clear that the drug was not triggering alpha to beta cell conversion, as the initial Cell paper had claimed.

The Cell paper suggested that the widely used anti-malaria drug artemether suppresses the α cell transcription factor Arx to promote transdifferentiation into β cells. However, key initial experiments in this paper were carried out in islet cell lines, and most subsequent validation experiments implied transdifferentiation without direct demonstration of α to β cell conversion.

 Indeed, the authors founnd no evidence that artemether promotes transdifferentiation of primary α cells into β cells. Moreover, artemether reduces Ins2 expression in primary β cells >100-fold, suppresses glucose uptake, and abrogates β cell calcium responses and insulin secretion in response to glucose.These observations suggest that artemether induces general islet endocrine cell dedifferentiation, 

The new paper highlights the importance of reproducibility, a perennial and hotly contested topic of concern at all levels of scientific research. It also demonstrates how routine lab assignments meant to educate students can provide the foundations for published research.

"It's important to realize that our work has an impact in the real world," senior author said. "We should continuously strive to hold ourselves and our peers to a higher standard, particularly when we talk about discoveries that promise a possible cure for diabetes."