A hormone produced and secreted by the liver as a previously unknown cause of insulin resistance has been identified by scientists.
The discovery may be a new target for the treatment of insulin resistance and type 2 diabetes.
"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," said Hirofumi Misu of Kanazawa University in Japan.
The researchers had discovered earlier that genes encoding secretory proteins are abundantly expressed in the livers of people with Type 2 diabetes.
Now, the researchers reported the results of comprehensive gene expression analyses, revealing that the liver expresses higher levels of the gene encoding selenoprotein P (SeP) in people with type 2 diabetes who are more insulin resistant.
Further studies in mice added support to the notion that the connection between SeP and insulin resistance is causal. When the researchers gave normal mice SeP, they became insulin resistant and their blood sugar levels rose.
A treatment that blocked the activity of SeP in the livers of diabetic and obese mice improved their sensitivity to insulin and lowered blood sugar levels.
Misu said that SeP was known previously as a protein produced mainly in the liver, where it transports the essential trace element selenium from the liver to other parts of the body.
But the protein's clinical significance and, more specifically, its role in glucose homeostasis weren't known.
In the development of insulin resistance, the researchers don't think SeP acts on its own.
"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," said the researchers.
The findings were published in the Cell Metabolism.