Joslin researchers clarify mechanisms for beta-cell formation

BOSTON A new study by researchers at Joslin Diabetes Center sheds light on the key mechanisms by which new pancreatic beta cells normally form in response to insulin resistance. These findings may some day help researchers devise ways of staving off full-blown diabetes.

Insulin resistance is a condition in which the body needs increasing amounts of insulin to function properly, including keeping blood glucose levels in the normal range. It is a major contributor to type 2 diabetes, obesity and the metabolic syndrome, which affect nearly one-quarter of the American population.

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, Rohit N. Kulkarni, M.D., Ph.D., Jonathon N. Winnay, and C. Ronald Kahn, M.D., of Joslin Diabetes Center in Boston; Ulupi S. Jhala Ph.D., of The Whittier Institute of the University of California in La Jolla, Calif.; Stan Krajewski Ph.D., at the Burnham Institute in La Jolla; and Marc Montminy M.D., Ph.D., at The Salk Institute for Biological Studies in San Diego, Calif., studied this compensatory growth in two different genetically engineered animal models of insulin resistance called IR/IRS-1 mice and LIRKO mice. Dr. Kahn is the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

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-

Contact: Marjorie Dwyer
Joslin Diabetes Center

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