Yokoi Norihide, Beppu Masayuki, Yoshida Eri, Hoshikawa Ritsuko, Hidaka Shihomi, Matsubara Toshiya, Shinohara Masami, Irino Yasuhiro, Hatano Naoya, Seino Susumu
Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan.
Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan ; Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, 650-0017 Japan.
Metabolomics. 2015;11(5):1277-1286. doi: 10.1007/s11306-015-0784-9. Epub 2015 Mar 12.
Biomarkers for the development of type 2 diabetes (T2D) are useful for prediction and intervention of the disease at earlier stages. In this study, we performed a longitudinal study of changes in metabolites using an animal model of T2D, the spontaneously diabetic Torii (SDT) rat. Fasting plasma samples of SDT and control Sprague-Dawley (SD) rats were collected from 6 to 24 weeks of age, and subjected to gas chromatography-mass spectrometry-based metabolome analysis. Fifty-nine hydrophilic metabolites were detected in plasma samples, including amino acids, carbohydrates, sugars and organic acids. At 12 weeks of age, just before the onset of diabetes in SDT rats, the amounts of nine of these metabolites (asparagine, glutamine, glycerol, kynurenine, mannose, n-alpha-acetyllysine, taurine, threonine, and tryptophan) in SDT rats were significantly different from those in SD rats. In particular, metabolites in the tryptophan metabolism pathway (tryptophan and kynurenine) were decreased in SDT rats at 12 weeks of age and later. The lower tryptophan and kynurenine levels in the prediabetic state and later were further confirmed by a replication study on SDT rats and by a longitudinal study on another animal model of T2D, the Otsuka Long-Evans Tokushima Fatty rat. Our data indicate that tryptophan and its metabolites are potential biomarkers for prediabetes and that tryptophan metabolism may be a potential target of intervention for treatment of the disease.
2型糖尿病（T2D）发病的生物标志物有助于在疾病早期进行预测和干预。在本研究中，我们使用T2D动物模型——自发性糖尿病鸟居（SDT）大鼠，对代谢物变化进行了纵向研究。收集6至24周龄的SDT大鼠和对照斯普拉格-道利（SD）大鼠的空腹血浆样本，并进行基于气相色谱-质谱联用的代谢组分析。在血浆样本中检测到59种亲水性代谢物，包括氨基酸、碳水化合物、糖类和有机酸。在12周龄时，即SDT大鼠糖尿病发作前，这些代谢物中的9种（天冬酰胺、谷氨酰胺、甘油、犬尿氨酸、甘露糖、N-α-乙酰赖氨酸、牛磺酸、苏氨酸和色氨酸）在SDT大鼠中的含量与SD大鼠显著不同。特别是，色氨酸代谢途径中的代谢物（色氨酸和犬尿氨酸）在12周龄及以后的SDT大鼠中减少。在SDT大鼠上进行的重复研究以及对另一种T2D动物模型——大冢长-艾氏糖尿病大鼠进行的纵向研究进一步证实了糖尿病前期及以后色氨酸和犬尿氨酸水平较低。我们的数据表明，色氨酸及其代谢物是糖尿病前期的潜在生物标志物，色氨酸代谢可能是该疾病治疗的潜在干预靶点。
