A new study analyzes rare tumors in which insulin-producing beta cells are produced in excess in order to find a "genetic recipe" for regenerating these cells. And the findings might change the current therapeutic practices for treating diabetes.
Additionally, recent studies have shown that beta cells also play a crucial role in the development of type 2 diabetes. For instance, a study that Medical News Todayreported on found that the release of pro-inflammatory proteins kills off insulin-producing beta cells in the early stages of type 2 diabetes.
But the "problem" with beta cells, medically speaking, is that they replicate in early childhood but cease to proliferate after that.
New research, however, carried out by scientists at the Icahn School of Medicine at Mount Sinai in New York City, NY, uncovers a "genomic recipe" for regenerating these key cells.
The study was led by Dr. Andrew Stewart, the director of the Diabetes, Obesity, and Metabolism Institute at the Icahn School of Medicine, and the
Studying rare tumors to fight diabetes
For the new research, Dr. Stewart and team analyzed a very rare type of benign tumor called insulinomas. These are "pancreatic beta cell adenomas" that secrete too much of the hormone insulin.
The tumors are small and proliferate slowly. The researchers used whole-exome and RNA-sequencing analysis to examine the genetic makeup of 38 such tumors.
Speaking to Medical News Today about the rationale for choosing to study insulinomas, Dr. Stewart said, "In order to discover drugs that would make human pancreatic beta cells regenerate in people with diabetes, we wanted to understand how human beta cells normally replicate."
"Unfortunately," he added, "human beta cells only replicate in the first year of life, so obtaining beta cells from babies is difficult. On the other hand, insulinomas [...] are a prefect model: they are rare, they are benign [...] tumors of the human beta cell[s], and make large amount of insulin, so much [that] they cause low blood glucose (hypoglycemia)."
Study co-author Carmen Argmann, Ph.D. - who is an associate professor of Genetics and Genomic Sciences at the Icahn School of Medicine - explains the methods used in the research.
She says, "[We] looked at millions of data points collected in rare human insulinomas to try and find an answer to a common disease, diabetes."
"We then computationally created two molecular pictures from that data, one from the insulinoma and one for the normal beta cell, and identified the critical differences that will hopefully lead to new ways to expand beta cell mass in diabetes patients."
Rare tumors reveal 'genomic recipe'
This approach revealed genetic mutations, variants, and dysregulation of epigenetic factors that together suggested to the researchers new genetic "candidates" for inducing the regeneration of beta cells.
In other words, as Dr. Stewart says, "For the first time, we have a genomic recipe - an actual wiring diagram in molecular terms that demonstrates how beta cells replicate."
Speaking to MNT about the findings, Dr. Stewart said, "We were surprised because we assumed we would find that a small number of genes would have mutations in insulinomas."
"In fact," he continued, "what we found was that 278 genes were mutated in insulinomas, and almost every insulinoma had a different set of mutated genes."
The findings build on previous achievements by the same team. In a paper referenced in the new study, Dr. Stewart and team showed that a drug called harmine can induce beta cell replication.
Harmine, the authors explain, is to this day the only class of drugs that has the therapeutic potential to make beta cells proliferate.
The new results not only confirmed these previous findings, but they also uncovered even more novel pathways for designing drugs that could induce beta cell regeneration.
"[We were] gratified because we were able to identify multiple new, drug-treatable pathways to human beta cell regeneration," Dr. Stewart told us. "Thus, our premise was that we would find a drug-treatable pathway or two, but in fact we found much more."
Dr. Dennis S. Charney, the Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine, also weighs in on the findings.
"We are excited and gratified by these remarkable results, which reveal an extraordinary array of new and validated pathways for diabetes drug development [...] It is truly an exciting set of discoveries for the field of diabetes."
Dr. Dennis S. Charney
In the future, Prof. Argmann says, the researchers "plan to explore clinical applications of these new findings."
"Beta cell regeneration," Dr. Stewart told us, "will be beneficial to both [type 1 and type 2 diabetes]. The next frontier for us, and for the diabetes community in general, [is] to develop ways to target these novel classes of beta cell regenerative drugs to the pancreatic beta cell."
"We and others are working hard on this," he concluded.