Tale of Two Mice Pinpoints Insulin Resistance Factor
C. Ronald Kahn, M.D.
Monday, May 16, 2011
The road to type 2 diabetes is paved with insulin resistance, in which the hormone begins to fail at its job helping to convert sugars to energy. Joslin researchers have now identified an enzyme called PKC-delta as an important molecular modifier for development of insulin resistance, diabetes and fatty liver in mice. They also have found evidence suggesting a similar role for the enzyme in humans, making PKC-delta a promising new target for drugs for diabetes and related ailments.
Investigators in the laboratory of C. Ronald Kahn, M.D., began with two existing strains of mice that are on opposite sides of the spectrum for insulin resistance.
“The ‘B6’ mouse is very prone to develop both obesity and diabetes, and the ‘129’ mouse is quite protected from both, even if it possesses a genetic defect in insulin signaling,” says Dr. Kahn, who is the Mary K. Iacocca Professor of Medicine at Harvard Medical School. “Comparing the two models, it’s as if there’s an on/off switch for insulin resistance and diabetes between them. We reasoned that if we could find out the differences between B6 and 129 mice, we could identify a factor that could be a major modifier of insulin resistance, and a good drug target for treatment of type 2 diabetes.”