How does insulin-like growth factor I protect liver function?

IGF-I has been shown to exert a mitochondrial protection in experimental cirrhosis leading to reduce caspase activation and apoptosis and increasing ATP production.

The study, performed by a team led by Dra. Castilla de Cortázar Larrea, is described in a research article to be published on May 7, 2008 in the World Journal of Gastroenterology.

IGF-I is an anabolic hormone produced mainly in the liver in response to growth hormone (GH) stimulation. In cirrhosis the reduction of receptors for GH in hepatocytes and the diminished synthesis ability of the hepatic parenchyma cause a progressive fall in serum IGF-I levels. The mechanisms of IGF-I activities regarding the improvement of liver function and fibrosis is not fully understood.

Mitochondria are a major source of reactive oxygen species (ROS) under physiologic conditions. Mitochondria are particularly sensitive to damage induced by ROS in the pathogenesis of disease. Recently, a large number of studies have associated mitochondrial dysfunction caused by ROS to both accidental cell death (necrosis) and programmed cell death (apoptosis).

The biochemical results in this series showed an improvement of liver function tests and a reduction of fibrosis and liver oxidative products were also observed in the animals treated with IGF.

MMP in state 3 and 4 was significantly decreased in the cirrhosis animals and was restored after IGF-I treatment. Mitochondria from untreated cirrhotic rats showed a significant increase of ROS generation as and cirrhotic rats treated with IGF-I. ATPase activity declined in untreated cirrhotic rats.The number of TUNEL-positive hepatocytes was significant increased in untreated cirrhotic group. IGF-I treatment reduced apoptosis in hepatocytes. Westen blotting for fragment-17 of caspasa 3 showed a significant increase of caspase 3 activation in untreated cirrhotic rats. However a notable reduction in the expression of this fragment was observed in cirrhotic animals treated with IGF-I.

In the view of the authors, this work provides new evidence of the beneficial effect of IGF-I supplementation in experimental liver cirrhosis and experimental basis for further studies at exploring the potential of IGF-I in the treatment of human cirrhosis.