Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
PLoS One. 2012;7(4):e34952. doi: 10.1371/journal.pone.0034952. Epub 2012 Apr 4.
We 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 FINDINGS: We 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/SIGNIFICANCE: These results suggest that overproduction of liver-derived secretory protein SeP is connected with hypoadiponectinemia in patients with type 2 diabetes.
我们最近发现硒蛋白 P(SeP)是一种肝脏来源的分泌蛋白,可导致肝脏和骨骼肌胰岛素抵抗;然而,尚不清楚 SeP 是否以及如何作用于脂肪组织。本研究检验了以下假设,即 SeP 与 2 型糖尿病患者的低脂联素血症有关。
方法/主要发现:我们比较了 36 例 2 型糖尿病患者血清 SeP 与脂联素和其他临床参数的水平。我们还测量了 SeP 敲除小鼠的血中脂联素水平。循环 SeP 水平与空腹血糖呈正相关(r = 0.35,P = 0.037),与 2 型糖尿病患者的总脂联素和高分子脂联素呈负相关(r = -0.355,P = 0.034;r = -0.367,P = 0.028)。SeP 是总脂联素和高分子脂联素的独立预测因子,与年龄、体重和定量胰岛素敏感性指数无关(β = -0.343,P = 0.022;β = -0.357,P = 0.017)。给予常规饮食或高蔗糖高脂肪饮食时,SeP 敲除小鼠的血中脂联素水平升高。
结论/意义:这些结果表明,肝脏来源的分泌蛋白 SeP 的过度产生与 2 型糖尿病患者的低脂联素血症有关。