Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Zaifu-5, Hirosaki Japan.
Diabetes Res Clin Pract. 2013 Jan;99(1):30-8. doi: 10.1016/j.diabres.2012.10.022. Epub 2012 Nov 5.
Cholesterol efflux with high-density lipoprotein (HDL) particles has an important role in the first step of reverse cholesterol transport (RCT). However, HDL function in type 2 diabetes has not been well investigated thoroughly. We measured cholesterol efflux in 36 patients with type 2 diabetes compared with 9 controls without diabetes.
The HDL fraction was separated with polyacrylamide gel and recovered using the protein recovery system. Concentration adjusted HDL fraction was used to determine HDL-mediated cholesterol efflux (Efflux-hdl) from THP-1 derived macrophages. We measured paraoxonase-1 (PON 1) activity to determine antioxidation capacity, serum amyloid A protein (SAA) to determine inflammatory response, and carboxymethyl-lysin (CML) to determine antiglucoxidative capacity.
Efflux-hdl demonstrated no correlation with plasma apoprotein A-1 (ApoA-I) or HDL-cholesterol in patients with diabetes. PON1 activity in the patients' HDL fraction was positively correlated with Efflux-hdl (r=0.39, p=0.02), and showed a negative tendency with HbA1c levels (r=-0.28, p=0.10). SAA and CML levels did not demonstrate correlation with Efflux-hdl in patients with diabetes.
We confirmed the functional changes in HDL particles in the patients. Efflux-hdl from macrophages was reduced depending upon the decrease in PON1 activity, which was inversely related to HbA1c levels.
高密度脂蛋白(HDL)颗粒介导的胆固醇外排对于胆固醇逆转运(RCT)的第一步具有重要作用。然而,2 型糖尿病患者的 HDL 功能尚未得到充分研究。我们测量了 36 例 2 型糖尿病患者与 9 例无糖尿病对照者的胆固醇外排。
使用聚丙烯酰胺凝胶分离 HDL 级分,并使用蛋白回收系统回收。调整浓度的 HDL 级分用于测定 THP-1 衍生巨噬细胞中 HDL 介导的胆固醇外排(Efflux-hdl)。我们测量对氧磷酶 1(PON1)活性以确定抗氧化能力,血清淀粉样蛋白 A 蛋白(SAA)以确定炎症反应,以及羧甲基赖氨酸(CML)以确定抗糖化氧化能力。
糖尿病患者的 Efflux-hdl 与血浆载脂蛋白 A-1(ApoA-I)或 HDL-胆固醇无相关性。患者 HDL 级分中的 PON1 活性与 Efflux-hdl 呈正相关(r=0.39,p=0.02),并且与 HbA1c 水平呈负相关趋势(r=-0.28,p=0.10)。糖尿病患者的 SAA 和 CML 水平与 Efflux-hdl 无相关性。
我们证实了患者 HDL 颗粒的功能变化。由于 PON1 活性降低,巨噬细胞的 Efflux-hdl 减少,与 HbA1c 水平呈负相关。