Liver Selenoprotein Linked to Insulin Resistance

Results presented in a recent publication link the liver-derived secretory protein selenoprotein P (SeP) to the development of insulin resistance, which characterizes type II diabetes.

SeP is a member of the liver hormone family known as hepatokines. Researchers had postulated that some hepatokines might be involved in glucose metabolism in a manner similar to the adipokines produced by fat tissue.

In the current study, published in the November 2010 issue of the journal Cell Metabolism, investigators at the Kanazawa University Graduate School of Medical Science (Japan) used serial analysis of gene expression (SAGE) and DNA chip methods to show that hepatic SeP mRNA levels correlated with insulin resistance in humans.

In cell cultures administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice.

The metabolic actions of SeP were found to be mediated, at least partly, by inactivation of the enzyme adenosine monophosphate-activated protein kinase (AMPK).

"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 first author Dr. Hirofumi Misu, assistant professor of disease control and homeostasis at Kanazawa University Graduate School of Medical Science. "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.”

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Kanazawa University Graduate School of Medical Science