The accumulation of fat in the liver (hepatic steatosis) can result in non-alcoholic fatty liver disease, which is associated with hepatic insulin resistance and type 2 diabetes mellitus. However, the mechanisms by which fat accumulation leads to hepatic insulin resistance have not been well characterized. Now, researchers from Yale University have shown that a protein known as PKC-epsilon has an important role in the development of fat-induced hepatic insulin resistance in rats
In the study, which appears online in advance of publication in the March print issue of the Journal of Clinical Investigation, Gerald Shulman and colleagues show that although specifically decreasing the expression of PKC-epsilon in the liver and white adipose tissue of rats did not decrease fat accumulation following 3 days on a high-fat diet, it did protect the rats from developing hepatic insulin resistance. Further analysis showed that PKC-epsilon interacts with the insulin receptor and inhibits signaling downstream of the insulin receptor, providing a molecular mechanism for the lack of hepatic insulin resistance in the rats expressing low levels of PKC-epsilon in the liver and white adipose tissue. This identification of PKC-epsilon as a mediator of hepatic steatosis-induced hepatic insulin resistance in rats provides a new potential target for the development of therapeutics to treat individuals with non-alcoholic fatty liver disease and type 2 diabetes mellitus.
TITLE: Inhibition of protein kinase C-epsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease
AUTHOR CONTACT:
Gerald I. Shulman
Yale University School of Medicine, New Haven, Connecticut, USA.
JCI table of contents -- February 22, 2006
Contact: Karen Honey
Journal of Clinical Investigation
Комментариев нет:
Отправить комментарий