'Fasting Signal' Offers Clues to Insulin Resistance in the Obese

Mar. 4 -- TUESDAY, March 3 (HealthDay News) -- A signal known to play a role during fasting also becomes active in the fat tissue of obese mice in the early stages of progression toward type 2 diabetes, say researchers. They also found that blocking this signal in fat tissue prevents insulin resistance in obese mice.

Previous research found that the CREB pathway keeps blood sugar in balance during fasting by triggering glucose production in the liver. It's also been found that excessive CREB activity in diabetes contributes to high blood sugar and insulin resistance.

In this new study, researchers at the Salk Institute for Biological Studies investigated whether CREB was important in mature fat tissues as well. They found that CREB activity in fat cells in obese mice encourages insulin resistance by lowering the production of a hormone called adiponectin and the insulin-sensitive glucose transporter 4 (GLUT4).

Obese mice genetically altered to lack CREB in fat cells became more sensitive to insulin and were also protected from the development of fatty liver and inflammation in fat tissue. CREB seemed relatively unimportant in healthy mice, but in obese mice, the signal appears to be "doing something more pathological."

The findings suggest the "stress of obesity activates CREB genes and contributes to insulin resistance," noted Marc Montminy and colleagues.

"Taken together, these results show that targeting therapies to adipose tissue and, in particular, to the CREB signaling system could have important therapeutic benefits in a variety of insulin-resistant states," the researchers concluded.

The study was published in the March issue of Cell Metabolism.

More information

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases has more about insulin resistance and pre-diabetes.

SOURCE: Cell Press, news release, March 3, 2009