PMID- 37569840 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20230814 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 15 DP - 2023 Aug 5 TI - Metabolomics of Type 2 Diabetes Mellitus in Sprague Dawley Rats-In Search of Potential Metabolic Biomarkers. LID - 10.3390/ijms241512467 [doi] LID - 12467 AB - 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. FAU - Ndlovu, Innocent Siyanda AU - Ndlovu IS AD - School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. FAU - Tshilwane, Selaelo Ivy AU - Tshilwane SI AUID- ORCID: 0000-0002-3549-4675 AD - Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria 0110, South Africa. FAU - Vosloo, Andre AU - Vosloo A AD - School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. FAU - Chaisi, Mamohale AU - Chaisi M AD - Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria 0110, South Africa. AD - Foundational Biodiversity Science, South African National Biodiversity Institute, Pretoria 0001, South Africa. FAU - Mukaratirwa, Samson AU - Mukaratirwa S AUID- ORCID: 0000-0001-6843-1497 AD - School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. AD - One Health Center for Zoonoses and Tropical Veterinary Medicine, School of Veterinary Medicine, Ross University, Basseterre KN0101, Saint Kitts and Nevis. LA - eng GR - 41011-2020./Ross University School of Veterinary Medicine/ GR - P2020/11/National Research Foundation/ PT - Journal Article DEP - 20230805 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Amino Acids) RN - 0 (Biomarkers) SB - IM MH - Male MH - Rats MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - Rats, Sprague-Dawley MH - Hypoglycemic Agents/pharmacology MH - *Diabetes Mellitus, Experimental/complications MH - Blood Glucose/metabolism MH - Metabolomics/methods MH - Amino Acids MH - Biomarkers PMC - PMC10419637 OTO - NOTNLM OT - Sprague Dawley rats OT - biomarkers OT - metabolic pathways OT - metabolomics OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2023/08/12 10:43 MHDA- 2023/08/14 06:41 PMCR- 2023/08/05 CRDT- 2023/08/12 01:12 PHST- 2023/07/15 00:00 [received] PHST- 2023/07/27 00:00 [revised] PHST- 2023/07/28 00:00 [accepted] PHST- 2023/08/14 06:41 [medline] PHST- 2023/08/12 10:43 [pubmed] PHST- 2023/08/12 01:12 [entrez] PHST- 2023/08/05 00:00 [pmc-release] AID - ijms241512467 [pii] AID - ijms-24-12467 [pii] AID - 10.3390/ijms241512467 [doi] PST - epublish SO - Int J Mol Sci. 2023 Aug 5;24(15):12467. doi: 10.3390/ijms241512467.