Scientists from the Prince Felipe Research Center (CIPF) and the Biomedical Research Center in Network for Diabetes and Associated Metabolic Diseases (CIBERDEM), led by Luke Noon, have demonstrated how insulin plays a key role in the process of liver repair during chronic damage.

According to the new study, published in PLOS Biology, insulin resistance  —a very common condition closely associated with metabolic disease and type 2 diabetes mellitus— would reduce the ability of stem cells to respond to liver damage and generate new cells to repair liver tissue.

Patients with metabolic disease are more susceptible to liver damage because they are unable to regenerate the liver correctly,” explains Noon.

The study supports, therefore, the hypothesis that the development of liver pathology in patients with metabolic disease could be driven by a failure in communication between different cell types involved in the regenerative response,” he adds.

The data from the study show that the loss of functionality of the stem cells is triggered by a decrease in the levels of FGF7, a signaling molecule produced cells of the scar tissue surrounding the stem cells. After the damage, FGF7 acts as a ‘repair signal’ sent by cells of the scar tissue to stem cells in order to direct the regenerative response.

‘Signs’ to repair the liver

The work reveals that, in the case of livers of insulin-resistant mouse models, scar tissue not only produces less FGF7, but also the sensitivity to FGF7 of stem cells is lower, which prevents proper communication between these two groups of cells, essential for the liver repair machinery.

Consistent with the results obtained from mice with insulin resistance, the elimination of a gene essential for insulin signaling in human liver cell lines also reduced the levels of FGF7 in scar tissue and caused a loss of its sensitivity to FGF7, reducing its ability to generate healthy tissue and heal.

This suggests that insulin resistance may favor tissue healing over the regeneration of tissue and it coincides with the increased incidence of scarring/liver fibrosis in patients with metabolic disease.

For Noon, the model “helps explaining the links already established between insulin resistance and chronic liver disease while also highlights the potential for future therapeutic interventions using FGF7 to promote liver repair.”

 

Source: SINC