School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria 0110, South Africa.
Int J Mol Sci. 2023 Aug 5;24(15):12467. doi: 10.3390/ijms241512467.
Type 2 diabetes mellitus (T2DM) is an expanding global health concern, closely associated with the epidemic of obesity. Individuals with diabetes are at high risk for microvascular and macrovascular complications, which include retinopathy, neuropathy, and cardiovascular comorbidities. Despite the availability of diagnostic tools for T2DM, approximately 30-60% of people with T2DM in developed countries are never diagnosed or detected. Therefore, there is a strong need for a simpler and more reliable technique for the early detection of T2DM. This study aimed to use a non-targeted metabolomic approach to systematically identify novel biomarkers from the serum samples of T2DM-induced Sprague Dawley (SD) rats using a comprehensive two-dimensional gas chromatography coupled with a time-of-flight mass spectrometry (GCxGC-TOF/MS). Fifty-four male Sprague Dawley rats weighing between 160-180 g were randomly assigned into two experimental groups, namely the type 2 diabetes mellitus group (T2DM) (n = 36) and the non-diabetic control group (n = 18). Results from this study showed that the metabolite signature of the diabetic rats was different from that of the non-diabetic control group. The most significantly upregulated metabolic pathway was aminoacyl-t-RNA biosynthesis. Metabolite changes observed between the diabetic and non-diabetic control group was attributed to the increase in amino acids, such as glycine, L-asparagine, and L-serine. Aromatic amino acids, including L-tyrosine, were associated with the risk of future hyperglycemia and overt diabetes. The identified potential biomarkers depicted a good predictive value of more than 0.8. It was concluded from the results that amino acids that were associated with impaired insulin secretion were prospectively related to an increase in glucose levels. Moreover, amino acids that were associated with impaired insulin secretion were prospectively related to an increase in glucose levels.
2 型糖尿病（T2DM）是一个不断扩大的全球健康问题，与肥胖症的流行密切相关。糖尿病患者发生微血管和大血管并发症的风险较高，包括视网膜病变、神经病变和心血管合并症。尽管有用于 T2DM 的诊断工具，但发达国家约有 30-60%的 T2DM 患者从未被诊断或发现。因此，需要一种更简单、更可靠的技术来早期发现 T2DM。本研究旨在使用非靶向代谢组学方法，使用全面的二维气相色谱与飞行时间质谱联用（GCxGC-TOF/MS），从 T2DM 诱导的 Sprague Dawley（SD）大鼠的血清样本中系统地识别新型生物标志物。54 只体重在 160-180g 之间的雄性 Sprague Dawley 大鼠被随机分为两组，即 2 型糖尿病组（T2DM）（n=36）和非糖尿病对照组（n=18）。该研究结果表明，糖尿病大鼠的代谢物特征与非糖尿病对照组不同。上调最显著的代谢途径是氨基酸酰基-t-RNA 生物合成。在糖尿病组和非糖尿病对照组之间观察到的代谢物变化归因于氨基酸（如甘氨酸、L-天冬酰胺和 L-丝氨酸）的增加。芳香族氨基酸，包括 L-酪氨酸，与未来高血糖和显性糖尿病的风险相关。鉴定出的潜在生物标志物的预测值大于 0.8。结果表明，与胰岛素分泌受损相关的氨基酸与血糖水平升高有前瞻性关系。此外，与胰岛素分泌受损相关的氨基酸与血糖水平升高有前瞻性关系。
