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Beta-cell proliferation seen with harmine compound from plant used in traditional medicine
A drug derived from a flowering plant found in the Middle East and in some South American vines appears to drive human insulin-producing beta cells to multiply, according to research published in Nature Medicine.
“Currently, there are many diabetes drugs, but none address the unmet clinical need to induce human beta-cell regeneration,” Andrew Stewart, MD, director, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine, told Endocrine Today.
Andrew Stewart
In a robotic high-throughput screen of more than 102,300 potential drugs, Stewart and colleagues discovered that harmine — from the perennial Harmal (peganum Harmala), already used in traditional medicine — led to sustained division and multiplication of adult human beta cells in culture.
“Our research defined harmine analogues that drive human beta-cell proliferation, and we also defined the mechanism within the beta cell through which harmine is able to regulate proliferation,” Stewart said.
In three groups of mice engineered to mimic diabetes in humans, harmine tripled beta-cell count and improved blood glucose control. The researchers found the compound recreated similar amounts of beta-cell division in cell and animal tests, according to a news release.
The investigators believe dual specificity tyrosine-regulated kinase-1a (DYRK1A) is the target of harmine; previous research demonstrated that the enzyme drives cell division in other cell types.
“We found that harmine, likely by interacting with DYRK1A, increases levels of other known drivers of cell division,” investigator Peng Wang, PhD, also in the department at Icahn School of Medicine, said in the release. “These drivers include the protein c-MYC, the gene which was the basis of the screen we used to identify harmine as a potential treatment.”
Peng Wang
In the experiments, when a compound activated the DNA snippet that activates c-MYC, a sensor would glow; harmine was among 86 that caused the brightest glow and the lone one to induce beta-cell multiplication.
The researchers are now focused on altering harmine and its relatives to find compounds that target only beta cells, according to the release.
“The reason that this work is published in a high-profile journal is that it provides the basis for rational drug design and discovery of a novel and unanticipated class of drugs that can actually make human beta cells replicate and expand in people with diabetes,” Stewart said. “Efforts to develop these drugs are underway. – by Allegra Tiver
Disclosure: The researchers report no relevant financial disclosures.