The UCSF Diabetes Center's Dr. Ira Goldfine and his team believe they have identified one of the major proteins causing insulin resistance and type 2 diabetes.

In a recent study published in the journal Diabetes, Goldfine reported that mice expressing the human version of the protein PC-1 in their liver have significantly elevated blood glucose levels and show 2-fold higher levels of insulin compared to controls. Animals with increased PC-1 protein levels have hyperglycemia, hyperinsulinemia and impaired glucose tolerance, all hallmark signs of type 2 diabetes.

PC-1 was first identified by Goldfine and colleague Betty Maddux in 1995, when they noted that it was present in greater abundance in patients with type 2 diabetes. Evidence that PC-1 might be involved in insulin resistance followed when they showed that in cultured cells, the protein binds to the insulin receptor, impairing the cells’ ability to utilize insulin.

This newly published study provides the first direct evidence that expression of PC-1 in animals is linked to insulin resistance and type 2 diabetes.

“This latest study makes a solid case that overexpression of PC-1 can cause type 2 diabetes,” says Goldfine. “While we have had strong suspicions for years, we now have direct evidence in animals that PC-1 can lead to insulin resistance and hyperglycemia.”

While this study examined PC-1 expression in the livers of mice, in humans, PC-1 is generally expressed in muscle and adipose (fat) tissue. Dr. Goldfine explained that one of their next tasks is to examine the effects of the protein in muscle cells, to further establish the link to human type 2 diabetes.

The entire research team is hopeful that, eventually, this discovery will lead to new therapies for the prevention and treatment of type 2 diabetes.

The research was published in the February 1 issue of Diabetes. Lead author of the publication was Hengjiang Dong of the Mt Sinai School of Medicine. Co-authors were: Jennifer Altomonte and Marcia Meseck also from Mt Sinai; Betty Maddux and Jack Youngren (UCSF); Domenico Accili (Columbia University); and Robert Terkeltaub and Kristen Johnson (UCSD).