Abstract
BackgroundWe recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes.Methodology/Principal FindingsWe compared serum levels of SeP with those of adiponectin and other clinical parameters in 36 patients with type 2 diabetes. We also measured levels of blood adiponectin in SeP knockout mice. Circulating SeP levels were positively correlated with fasting plasma glucose (r = 0.35, P = 0.037) and negatively associated with both total and high-molecular adiponectin in patients with type 2 diabetes (r = −0.355, P = 0.034; r = −0.367, P = 0.028). SeP was a predictor of both total and high-molecular adiponectin, independently of age, body weight, and quantitative insulin sensitivity index (β = −0.343, P = 0.022; β = −0.357, P = 0.017). SeP knockout mice exhibited an increase in blood adiponectin levels when fed regular chow or a high sucrose, high fat diet.Conclusions/SignificanceThese results suggest that overproduction of liver-derived secretory protein SeP is connected with hypoadiponectinemia in patients with type 2 diabetes.
Highlights
We have recently identified selenoprotein P (SeP) as a liverderived secretory protein that causes insulin resistance and hyperglycemia in patients with type 2 diabetes [1]
Circulating selenoprotein P is associated with fasting plasma glucose and total and high-molecular adiponectin levels in patients with type 2 diabetes
The results indicate that circulating SeP, a liver-derived secretory protein, is an independent predictor of adiponectin in patients with type 2 diabetes
Summary
We have recently identified selenoprotein P (SeP) as a liverderived secretory protein that causes insulin resistance and hyperglycemia in patients with type 2 diabetes [1]. We have found that blood levels of SeP are elevated in rodents and patients with type 2 diabetes, and that SeP impairs cellular insulin signal transduction and dysregulates glucose metabolism in both hepatocytes and myocytes, at least partly, by inactivating adenosine monophosphateactivated protein kinase (AMPK). These findings suggest that SeP functions as a ‘‘hepatokine’’ causing insulin resistance in the liver and skeletal muscle of patients with type 2 diabetes. We recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes
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