Nakamura Kazuo, Yamagishi Sho-Ichi, Adachi Hisashi, Kurita-Nakamura Yayoi, Matsui Takanori, Inoue Hiroyoshi
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Diabetes Metab Res Rev. 2009 Jan;25(1):52-6. doi: 10.1002/dmrr.820.
Pigment epithelium-derived factor (PEDF) inhibits endothelial cell injury. Further, serum levels of PEDF are elevated in the metabolic syndrome. These observations suggest that PEDF may be elevated as a counter-system against vascular cell damage in the metabolic syndrome. However, little is known about the regulation of PEDF in patients with diabetes. In order to clarify the determinants of serum PEDF, here, we examined the relationship between the 1-year changes in PEDF levels and those in anthropometric and metabolic variables in type 2 diabetic patients.
Eighty-six consecutive outpatients with type 2 diabetes underwent a complete history and physical examination, determination of blood chemistries, and serum levels of PEDF at baseline and 1 year after. PEDF gene expression in cultured subcutaneous or omental adipocytes were analysed by quantitative real-time reverse transcription-polymerase chain reactions.
Multiple regression analyses revealed that waist circumference, triglycerides, creatinine, and TNF-alpha were independently associated with PEDF. Further, the percent changes in serum levels of PEDF during 1-year observational periods were positively correlated with those of BMI. In addition, PEDF mRNA levels in cultured adipocytes were increased in parallel to the BMI values of subjects from whom adipocytes were derived, especially in omental adipocytes.
These results demonstrated that serum levels of PEDF were positively associated with metabolic components and TNF-alpha in Japanese patients with type 2 diabetes. Our present study suggests that PEDF may be generated from adipose tissues and play some role in visceral obesity in type 2 diabetic patients.
色素上皮衍生因子(PEDF)可抑制内皮细胞损伤。此外,代谢综合征患者血清中PEDF水平会升高。这些观察结果表明,PEDF水平升高可能是代谢综合征中对抗血管细胞损伤的一种代偿机制。然而,对于糖尿病患者中PEDF的调节机制知之甚少。为了阐明血清PEDF的决定因素,我们在此研究了2型糖尿病患者PEDF水平的1年变化与人体测量及代谢变量变化之间的关系。
86例连续的2型糖尿病门诊患者接受了完整的病史和体格检查,测定了血液生化指标,并在基线和1年后检测了血清PEDF水平。通过定量实时逆转录-聚合酶链反应分析培养的皮下或网膜脂肪细胞中PEDF基因的表达。
多元回归分析显示,腰围、甘油三酯及肌酐水平以及肿瘤坏死因子-α(TNF-α)与PEDF独立相关。此外,1年观察期内血清PEDF水平的百分比变化与体重指数(BMI)的变化呈正相关。此外,培养的脂肪细胞中PEDF mRNA水平与所取脂肪细胞供体的BMI值呈平行升高,尤其是在网膜脂肪细胞中。
这些结果表明,在日本2型糖尿病患者中,血清PEDF水平与代谢成分及TNF-α呈正相关。我们目前的研究提示,PEDF可能由脂肪组织产生,并在2型糖尿病患者的内脏肥胖中发挥一定作用。