Circulating ApoJ is closely associated with insulin resistance in human subjects.

Circulating ApoJ is closely associated with insulin resistance in human subjects.
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DOI:
10.1016/j.metabol.2017.09.014
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发表时间:
2018-01
期刊:
Metabolism: clinical and experimental
影响因子:
--
通讯作者:
Kim YB
Kim YB
中科院分区:
其他
文献类型:
--
作者:
Seo JA;Kang MC;Ciaraldi TP;Kim SS;Park KS;Choe C;Hwang WM;Lim DM;Farr O;Mantzoros C;Henry RR;Kim YB

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胰岛素抵抗是2型糖尿病的主要危险因素。载脂蛋白J(ApoJ)与包括心血管疾病和阿尔茨海默病在内的病理生理状态改变有关。然而,ApoJ在葡萄糖稳态调节中的功能仍不清楚。本研究旨在确定血清ApoJ水平是否与人类受试者的胰岛素抵抗相关,以及在改善胰岛素敏感性的干预措施后是否发生变化。在非糖尿病(ND)和2型糖尿病(T2 D)受试者中评估血清ApoJ水平和胰岛素抵抗状态。在一个单独的T2 D受试者队列中评价了罗格列酮或二甲双胍治疗对高胰岛素/正常血糖钳夹期间血清ApoJ水平和葡萄糖处置率(GDR)的影响。通过免疫印迹或ELISA测量总ApoJ蛋白或与HDL和LDL组分相关的ApoJ蛋白。T2 D受试者的空腹血清ApoJ水平显著升高(ND vs T2 D; 100±8.3 vs. 150.6±8.5 Au,P <0.0001)。循环ApoJ水平与空腹血糖、空腹胰岛素、HOMA-IR和BMI密切相关。ApoJ水平与HOMA-IR显著独立相关,即使在校正年龄、性别和BMI后也是如此。罗格列酮治疗T2 D受试者导致血清ApoJ水平降低(治疗前vs.治疗后; 100±13.9 vs. 77±15.2 Au,P=0.015),而二甲双胍对ApoJ水平无影响。治疗期间ApoJ水平的变化与GDR的变化呈负相关。有趣的是,LDL组分中的ApoJ含量与HOMA-IR呈负相关。血清ApoJ水平与胰岛素抵抗的程度密切相关,与肥胖无关,并且在2型糖尿病中仅响应于罗格列酮而沿着胰岛素抵抗的改善。
Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer’s disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100±8.3 vs. 150.6±8.5 AU, P <0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100±13.9 vs. 77±15.2 AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes.
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