Hidden Mechanism In Rare Benign Tumors Key To Diabetes Drug
Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Normal physiologic human beta cell replication occurs only transiently in human infancy and early childhood, ceasing irreversibly thereafter. Therapeutically, there is only one class of drugs, still in early development, that reproducibly induces human beta cell replication. Even here, however, the replication rates induced are modest and not beta cell-specific.
Now, researchers at the Icahn School of Medicine at Mount Sinai have reasoned that insulinomas hold the “genomic recipe” for beta cell expansion.
Insulinomas are very rare, small (~ 1–2 cm), slowly proliferating pancreatic beta cell adenomas. They are almost always benign, and are readily treated by laparoscopic removal. These tumors usually come to medical attention through their overproduction of insulin, causing hypoglycemia, with resultant psychomotor symptoms.
Therefore, the researchers used this adenoma as a model to study insulin secretion pathways. They collected 38 human insulinomas- rare pancreatic tumors that secrete too much insulin- and analyzed their genomics and expression patterns.
They then carried out network analysis of the data to computationally model relevant molecular events in insulinoma, relative to
normal adult and juvenile human beta cells. “Our primary intent was to employ an integrative genomics approach to identify mitogenic mechanisms with potential application for human beta cell expansion,” the authors write in their published paper in Nature Communications.“For the first time, we have a genomic recipe- an actual wiring diagram in molecular terms that demonstrates how beta cells replicate,” Dr. Andrew Stewart, director of the Diabetes, Obesity, and Metabolism Institute at the Icahn School of Medicine, said in a press release.
The key is knowing how to look, not just where to look, adds co-author Carmen Argmann, Ph.D., associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai. “In this case, 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.”
The researchers next plan to look for clinical applications of their findings in partnership with Sema4, a genomic testing firm spun out of the Mount Sinai Health System. Sema4 is an interdisciplinary partnership of scientists, doctors, engineers, and genetic counselors that focuses on merging big data analytics with clinical diagnostics to aid disease treatment, diagnosis, and prevention.
