Liver Protein Causes Insulin Resistance

A hormone that is produced and secreted by the liver, is one of the causes of insulin resistance in type 2 diabetes patients, found a team of researchers from Kanazawa University Graduate School of Medical Science in Japan.

This is the first time that a link between this protein and insulin resistance is found, even though the researchers had discovered earlier that genes encoding secretory proteins are highly expressed in the livers of people with type 2 diabetes.

This earlier discovery was actually what pushed Hirofumi Misu and colleagues to start thinking that, just like fat tissue, the liver could help the development of type 2 diabetes and insulin resistance through secretory proteins called 'hepatokines'.

After a thorough research, the results reveal that people with type 2 diabetes who are more insulin resistant than others, have higher levels of the gene encoding selenoprotein P (SeP) in their liver, as well as increased blood levels of SeP.

Once the team experimented in mice, they found out that normal mice who were given SeP, became insulin resistant, and their blood sugar levels rose.

This means that SeP is causing the insulin resistance, so a treatment that can block the activity of SeP in the livers of diabetic and obese mice, can also improve their sensitivity to insulin and lower their blood sugar levels.

Even though the researchers knew that SeP was mainly produced in the liver, so that it could transport selenium to other parts of the body, its role in glucose homeostasis was unidentified.

Hirofumi Misu said that “the current study sheds light on a previously underexplored function of the liver; the liver participates in the pathogenesis of insulin resistance through hormone secretion.”

This opens the way to a new target for the treatment of type 2 diabetes and insulin resistance, even though the SeP is not acting alone.

The researchers say that fat tissue is a main contributor to the development of insulin resistance by the fat-derived hormones called adipokines it produces, and as the team say they have preliminary evidence of this connection, all it takes now is further investigation.

“Our study raises the possibility that the liver functions as an endocrine organ by producing a variety of hepatokines and that the dysregulation or impairment of hepatokine production might contribute to the development of various diseases,” Misu and his colleague Toshinari Takamura add.

The findings appear in the November issue of Cell Metabolism, a Cell Press publication.