Activation of p53 enhances apoptosis and insulin resistance in a rat model of alcoholic liver disease.

ABSTRACT:

Background & aims

Chronic ethanol consumption in the Long-Evans (LE) rat has been associated with hepatic p53 activation, and inhibition of the insulin/PI3K/AKT signal transduction cascade due to increased expression of PTEN. We hypothesize that p53 activation and altered insulin signaling may influence the susceptibility of rats to ethanol-induced liver damage. Furthermore, p53 not only activates programmed cell death pathways and suppresses hepatocellular survival signals, but also promotes gluconeogenesis to increase systemic insulin resistance due to a novel metabolic function.

Methods

Fischer (F), Sprague-Dawley (SD) and LE rats were fed ethanol-containing or control liquid diet for 8 weeks. Histopathological and biochemical changes were assessed.

Results

Here, w

SUBMITTER: Derdak Z 

PROVIDER: S-EPMC2994971 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature