JDRF Research

Tumor-Suppressing Protein  Regulates Beta Cell Growth

JDRF researchers at Stanford University have found that a protein known to suppress tumors also plays a role in restraining insulin-producing beta cells from multiplying – raising the possibility that a therapy aimed at reducing levels of that protein could regenerate beta cells in people with diabetes.

The protein, menin, was already known to play a role in preventing cancer in the pancreas and other organs by tamping down the growth of new cells.  The Stanford finding suggests that menin is naturally reduced by hormones during pregnancy so beta
cells can expand to produce more insulin in response to increased body mass.

The discovery, made in mice by Seung Kim, Satyajit Karnik, and colleagues, is published in the journal Science.

The finding helps solve a puzzle that has baffled doctors—why 2 to 5 percent of women develop diabetes temporarily while pregnant, a condition called gestational diabetes. The research suggests that gestational diabetes occurs when the body does not adequately reduce menin production during pregnancy.

To test menin’s role in gestational diabetes, the researchers created mice that overproduce the hormone. When these mice became pregnant, the islets couldn’t grow sufficiently and the animals developed diabetes.

The researchers also showed that a hormone called prolactin, which is abundant in pregnant women, naturally represses menin levels and stimulates beta cell growth.  When they gave prolactin to nonpregnant mice, menin levels dropped and beta cell mass increased.

Understanding how menin is regulated could help researchers design therapies that spur the growth of insulin-producing beta cells, increasing insulin production and enabling people with type 1 diabetes to improve control of blood sugar levels.

To follow up on this finding, JDRF is funding Dr. Kim and Mathhew Meyerson, of Harvard Medical School, with an Academic Research and Development grant. The aims of the follow-up project are to validate this role for menin in humans and identify peptides that inhibit menin’s actions. This will allow researchers to test if inhibiting menin might be a safe, effective means of expanding beta cell mass in people.