Despite the knowledge on insulin, the molecular mechanisms in the liver that maintain blood glucose levels within tight limits are not fully understood. Two papers in September 13 Nature show that the transcriptional coactivator PGC-1 is a key molecule in the mechanism of liver glucose response to fasting and suggest that this pathway may be defective in type 1 and type 2 diabetes.
Yoon and colleagues from Dana-Farber Cancer Center, Harvard Medical School, Boston, Massachusetts found that PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency. In addition, induced expression of PGC-1 in hepatocytes strongly activates the glucose producing enzymes, leading to increased glucose output (
In a separate study, Stephan Herzig and colleagues from the Salk Institute for Biological Studies, La Jolla, California found that mice carrying a targeted disruption of the cyclic AMP...