New Beta Cells Form in Response to Insulin Resistance

New study sheds light on the key mechanisms by which new pancreatic beta cells normally form in response to insulin resistance. For years, the body compensates for insulin resistance in order to delay the onset of clinical type 2 diabetes: The pancreas secretes more insulin and, in fact, more insulin-producing beta cells form within the pancreas. This formation of new beta cells is the focus of intensive research: Which cells give rise to these new beta cells and how? (Some researchers, for example, theorize that the new cells are derived from immature ductal cells–the cells that line the ducts of the pancreas.) And what signals this replication of beta cells to occur?

To study these questions, the Joslin Diabetes Center in Boston; studied this compensatory growth in two different genetically engineered animal models of insulin resistance called IR/IRS-1 mice and LIRKO mice.

The results of immunohistochemical staining suggest that these new beta cells are not derived from duct cells. Rather, the beta-cell growth in insulin-resistant states occurs by "epithelial-to-mesenchymal transition," a mechanism in which cells take on a more primitive form and begin replicating. It is possible that the response originates from potential beta-cell stem cells, a more primitive cell that has yet to differentiate into a beta cell. They also showed that insufficiency of a protein called PDX-1, which is critical for the development of pancreatic islets that contain beta cells, limited the growth response in insulin-resistant states–suggesting that PDX-1 likely plays an important role in regulating this growth.

"Our paper clearly demonstrates a potential mechanism for beta-cell growth during insulin resistance, which in turn, occurs as a normal protective response to delay the onset of type 2 diabetes in obese and other susceptible individuals," says Dr. Kulkarni, an Investigator in the Cellular and Molecular Physiology Section at Joslin. September 2004 issue of The Journal of Clinical Investigation.

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