research frontline e-newsletter, april 2010

Scientists have identified a gene needed for cells to develop into insulin-producing beta cells, gaining an important new insight into beta cell development. The hope is that by better understanding this process, researchers may one day be able to harness it to either regenerate insulin-producing cells or to create an unlimited supply of them for use in beta cell replacement therapies like islet transplantation.

In the study, which was co-funded by JDRF, scientists learned that the gene Rfx6 plays a key role in beta cell development. They showed that mice lacking the gene failed to generate insulin-producing beta cells and most other normal cell types in the pancreatic islets. They also found that, in people, an Rfx6 deficiency results in diabetes; genetic tests showed that newborns deficient in Rfx6 completely lacked insulin-producing beta cells and other pancreatic hormone-producing cells.

The researchers also determined that Rfx6 expression is dependent on another gene called neurogenin 3, which plays a key role in the maturation of beta cells during embryonic development. Mice lacking neurogenin 3 quickly develop diabetes.

Although scientists do not fully understand how pancreatic cells mature into functional beta cells, this study identifies Rfx6 as a key part of the developmental process.

"Understanding the expression of this gene can help us produce cells for beta cell replacement therapies and may provide a marker to help develop therapeutics for regenerating, or regrowing, beta cells in people with diabetes," said Julia Greenstein, Director of JDRF's Beta Cell Therapies program. "This work also highlights the value of JDRF's support of basic research in pancreas development - how it can help direct us toward a cure for type 1 diabetes."

The study was published in the journal Nature and led by principal investigators Michael S. German from the University of California, San Francisco, and Constantin Polychronakos from McGill University in Montreal.

Key Point: JDRF-funded scientists have identified a gene that is required for cells to differentiate, or mature, into insulin-producing beta cells and other cell types in the pancreas. The research adds to the body of knowledge about beta cell development and thus enhances the potential for scientists to develop ways to restore the body's ability to make insulin.