Genetic study reveals how endocrine cell types are produced in the pancreas

This work, published March 6, 2007 in the journal Developmental Cell, sheds new light on the mechanism by which insulin-producing beta cells are generated in the pancreas, and may open the door to new treatment avenues for type 1 diabetes.

The pancreas plays a critical role in our ability to convert food into fuel. Type 1 diabetes is a chronic (lifelong) disease in which beta cells in the pancreas lose their ability to produce the amounts of insulin needed to control blood sugar levels. Those afflicted suffer reduced quality of life and risk life-threatening complications from the disease. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Type 1 diabetes accounts for 5 percent to 10 percent of all diagnosed cases of diabetes and has no cure. Insulin injections provide treatment, but their effectiveness is limited.

One possible avenue for treatment would be to restore the insulin-producing cells in the pancreas. But relatively little is known about how the body produces these cells during development and how the cells are regenerated in adults. Scientists do know that all pancreatic endocrine cells, including insulin-producing beta cells, arise from a single line of “progenitor cells” that express the gene Neurogenin 3.

The experiments carried out by researchers from the Swiss Institute for Experimental Cancer Research and EPFL, in collaboration with INSERM and Vanderbilt University, used transgenic mice to explore the stages by which the different endocrine cell types, including insulin-producing beta cells, are produced from the progenitor cells. They showed that the trigger causing progenitor cells to switch from generating one cell type to generating another does not require signals from cells surrounding the progenitors.

By pinpointing the mechanisms involved in the different stages of endocrine cell production, this work sheds new light on when and how insulin-producing beta cells are generated in the pancreas. These experiments should help the future identification of a molecule responsible for the ability to generate beta cells, and might lead to techniques to restore these cells in individuals with type 1 diabetes.