Genetically Altered Mouse Shows Ability to Regenerate Beta Cells

Author:  Neil Majithia
Institution:  Virginia Commonwealth University
Date:  July 2008

A research team at University of Texas Southwestern Medical Center has genetically engineered a mouse capable of regenerating pancreatic beta cells. The study, which is scheduled to appear in a future issue of Diabetes, provides insight for scientists working on ways to treat diabetes, and brings hope to the estimated 171 million people suffering from the disease worldwide.

The investigators induced death of the insulin-producing pancreatic beta cells before engineering the mouse model's regenerative ability. This occurs naturally in patients with type 1 diabetes (when beta cells are destroyed by immune system malfunction) and type 2 diabetes (when beta cells die from working too hard). Beta cells synthesize and release insulin into the bloodstream, where it promotes the absorption of glucose into tissues. If the beta cells are dead, however, no insulin is being produced, blood glucose levels rise, and a condition called hyperglycemia results.

"The ability to induce cell death is not novel. The fact that the beta cells regenerate after we kill them is really the new aspect of the model," said Dr. Philipp Scherer, professor of internal medicine and senior author of the study.

Scherer's team genetically altered mature pancreatic beta cells in the mice so that they would die when treated by a certain drug. However, when they stopped administering the drug, they found that the cells had started to regenerate. After two months, blood glucose levels in the mice were back to normal.

The regenerative effects of the genetically manipulated beta cells still remain a mystery, and the group is currently working to isolate the regenerative cell population. Devising the mechanism behind the regeneration could play a key role in future diabetes research, especially type 1 diabetes, for which there is currently no cure or preventative measure.

"This model allows us to get a transcriptional signature, a fingerprint, of how beta cells fend off the pharmaceutical stimulus we provide to prompt cell death," Dr. Scherer said. "In other words, it provides a way to identify the most critical factors that protect against beta cell death and to potentially find ways to increase these factors in people with type 1 diabetes."

Dr. Scherer hopes his findings will also aid in understanding more temporary conditions of hyperglycemia, such as those associated with gestational diabetes. Gestational diabetes occurs in pregnant women who have no prior history of diabetes, and while the hyperglycemic effects usually disappear after pregnancy, it is still unclear whether or not any permanent damage is done to blood vessels.

While the World Health Organization estimates that over 171 million people suffer from diabetes worldwide, that figure is expected to double by the year 2030, making diabetes an important area of research for biomedical scientists.

Written by Neil Majithia

Reviewed by Brittany Raffa

Published by Pooja Ghatalia.