THURSDAY, Jan. 24 (HealthDay News) -- The TNF-like weak inducer of apoptosis (TWEAK) protein induces insulin resistance in hepatocytes by interfering with the actions of insulin, according to a report published online Jan. 3 in Endocrinology.
Feng Feng, from the University of Adelaide in Australia, and colleagues examined the effect of TWEAK on insulin signaling in human hepatocarcinoma cells and rat hepatocytes.
The researchers found that TWEAK induced insulin resistance through inhibition of early insulin receptor signaling and downstream insulin signaling. The inhibition involved the TWEAK receptor Fn14 and alterations in signaling and phosphorylation of various other molecules. TWEAK treatment also blocked the ability of insulin to reduce the expression of gluconeogenic enzymes and increase glycogen synthesis.
"Therefore, these findings not only reveal a novel pathophysiological function of TWEAK/Fn14, but also uncover a new player that may contribute to the development of cellular insulin resistance in hepatocytes," Feng and colleagues conclude.
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