Singlet Oxygen Induced Products of Linoleates, 10-and 12-(Z,E)- Hydroxyoctadecadienoic Acids (HODE), Can Be Potential Biomarkers for Early Detection of Type 2 Diabetes
Singlet Oxygen Induced Products of Linoleates, 10-and 12-(Z,E)- Hydroxyoctadecadienoic Acids (HODE), Can Be Potential Biomarkers for Early Detection of Type 2 Diabetes
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DOI：
10.1371/journal.pone.0063542
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发表时间：
2013-05-15
期刊：
影响因子：
3.7
通讯作者：
Yoshida, Yasukazu
中科院分区：
文献类型：
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作者：
Umeno, Aya;Shichiri, Mototada;Yoshida, Yasukazu
目前的诊断测试，如血糖指标，在早期发现导致糖尿病的糖耐量受损（IGT）方面存在局限性。由各种氧化剂以随机和破坏性的方式诱导的氧化应激被认为在许多人类紊乱和疾病（如糖耐量受损）的病理生理学中起重要作用。我们开发了一种改进的测量体内脂质过氧化的方法，其中8-异前列腺素F-2 α(8-异- pgf (2 α))，羟基十八烯二烯酸（HODEs），羟基二烯酸（HETEs）和7-羟基胆固醇（7-OHCh）的存在，以及它们的母体分子，亚油酸（LA）和胆固醇（Ch），通过LC-MS/MS（8-异- pgf (2 α)， HODE和HETE）和GC-MS (7-OHCh， LA，三苯基膦还原和氢氧化钾皂化后的Ch)。然后，我们将该方法应用于志愿者（n = 57），包括正常型（n = 43）、“高正常”型（空腹血糖100-109 mg/dL， n = 7）、糖尿病前期型（IGT, n = 5）和糖尿病型（n = 2）通过口服葡萄糖耐量试验（ogts）诊断的受试者。OGTT期间测量血浆中的几种生物标志物，如胰岛素、瘦素、脂联素、白细胞介素-6、肿瘤坏死因子-a、高敏c反应蛋白、HbA1c和葡萄糖水平。我们发现空腹（10-和12-(Z，E)- hode）/LA水平随着OGTT期间HbA1c和葡萄糖水平的升高以及胰岛素分泌和抵抗指数的升高而显著升高。综上所述，10-和12-(Z，E)- hode可能是早期检测IGT和无OGTT的“高正常”型的重要生物标志物。
Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF(2 alpha), HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), "high-normal'' (fasting plasma glucose, 100-109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-a, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)-HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10-and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and "high-normal'' type without OGTT.