Metabolomics (Non-Targeted) of Induced Type 2 Diabetic Sprague Dawley Rats Comorbid with a Tissue-Dwelling Nematode Parasite

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Dec 23

PMID 38139040

Authors

Innocent Siyanda Ndlovu

Selaelo Ivy Tshilwane

Philile Ignecious Ngcamphalala

Andre Vosloo

Mamohale Chaisi

Samson Mukaratirwa

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes is a non-communicable metabolic syndrome that is characterized by the dysfunction of pancreatic β-cells and insulin resistance. Both animal and human studies have been conducted, demonstrating that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, there is a paucity of information on the impact that helminths have on the metabolome of the host and how the infection ameliorates T2DM or its progression. Therefore, this study aimed at using a non-targeted metabolomics approach to systematically identify differentiating metabolites from serum samples of T2DM-induced Sprague Dawley (SD) rats infected with a tissue-dwelling nematode, , and determine the metabolic pathways impacted during comorbidity. Forty-five male SD rats with a body weight between 160 g and 180 g were used, and these were randomly selected into control (non-diabetic and not infected with ) (n = 15) and T2DM rats infected with (TzDM) (n = 30). The results showed metabolic separation between the two groups, where d-mannitol, d-fructose, and glucose were upregulated in the TzDM group, when compared to the control group. L-tyrosine, glycine, diglycerol, L-lysine, and L-hydroxyproline were downregulated in the TzDM group when compared to the control group. Metabolic pathways which were highly impacted in the TzDM group include biotin metabolism, carnitine synthesis, and lactose degradation. We conclude from our study that infecting T2DM rats with a tissue-dwelling nematode, , causes a shift in the metabolome, causing changes in different metabolic pathways. Additionally, the infection showed the potential to regulate or improve diabetes complications by causing a decrease in the amino acid concentration that results in metabolic syndrome.

References

Wild S, Roglic G, Green A, Sicree R, King H . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047-53. DOI: 10.2337/diacare.27.5.1047. View

Thabet H, Saleh N, Thabet S, Abdel-Aziz M, Kalleny N . Decreased basal non-insulin-stimulated glucose uptake by diaphragm in streptozotocin-induced diabetic mice infected with Schistosoma mansoni. Parasitol Res. 2008; 103(3):595-601. DOI: 10.1007/s00436-008-1016-2. View

Farrell S, Coffeng L, Truscott J, Werkman M, Toor J, de Vlas S . Investigating the Effectiveness of Current and Modified World Health Organization Guidelines for the Control of Soil-Transmitted Helminth Infections. Clin Infect Dis. 2018; 66(suppl_4):S253-S259. PMC: 5982801. DOI: 10.1093/cid/ciy002. View

Ndlovu I, Tshilwane S, Vosloo A, Chaisi M, Mukaratirwa S . Metabolomics of Type 2 Diabetes Mellitus in Sprague Dawley Rats-In Search of Potential Metabolic Biomarkers. Int J Mol Sci. 2023; 24(15). PMC: 10419637. DOI: 10.3390/ijms241512467. View

Tuei V, Maiyoh G, Ha C . Type 2 diabetes mellitus and obesity in sub-Saharan Africa. Diabetes Metab Res Rev. 2010; 26(6):433-45. DOI: 10.1002/dmrr.1106. View

Ren W, Rajendran R, Zhao Y, Tan B, Wu G, Bazer F . Amino Acids As Mediators of Metabolic Cross Talk between Host and Pathogen. Front Immunol. 2018; 9:319. PMC: 5835074. DOI: 10.3389/fimmu.2018.00319. View

Hu F, Satija A, Manson J . Curbing the Diabetes Pandemic: The Need for Global Policy Solutions. JAMA. 2015; 313(23):2319-20. PMC: 5291074. DOI: 10.1001/jama.2015.5287. View

du Preez I, Loots D . New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa. Tuberculosis (Edinb). 2013; 93(3):330-7. DOI: 10.1016/j.tube.2013.02.008. View

Berbudi A, Ajendra J, Wardani A, Hoerauf A, Hubner M . Parasitic helminths and their beneficial impact on type 1 and type 2 diabetes. Diabetes Metab Res Rev. 2015; 32(3):238-50. DOI: 10.1002/dmrr.2673. View

10.

Jafarnejad A, Bathaie S, Nakhjavani M, Hassan M, Banasadegh S . The improvement effect of L-Lys as a chemical chaperone on STZ-induced diabetic rats, protein structure and function. Diabetes Metab Res Rev. 2007; 24(1):64-73. DOI: 10.1002/dmrr.769. View

11.

Zheng Y, Ley S, Hu F . Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2017; 14(2):88-98. DOI: 10.1038/nrendo.2017.151. View

12.

Rajamanickam A, Munisankar S, Dolla C, Menon P, Thiruvengadam K, Nutman T . Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis. PLoS Negl Trop Dis. 2020; 14(3):e0008101. PMC: 7069638. DOI: 10.1371/journal.pntd.0008101. View

13.

Rodriguez Melendez R . [Importance of biotin metabolism]. Rev Invest Clin. 2000; 52(2):194-9. View

14.

Onkoba N, Chimbari M, Kamau J, Mukaratirwa S . Metabolic and adaptive immune responses induced in mice infected with tissue-dwelling nematode . Open Vet J. 2016; 6(3):178-184. PMC: 5116437. DOI: 10.4314/ovj.v6i3.6. View

15.

Alonso A, Marsal S, Julia A . Analytical methods in untargeted metabolomics: state of the art in 2015. Front Bioeng Biotechnol. 2015; 3:23. PMC: 4350445. DOI: 10.3389/fbioe.2015.00023. View

16.

Basciano H, Federico L, Adeli K . Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond). 2005; 2(1):5. PMC: 552336. DOI: 10.1186/1743-7075-2-5. View

17.

Mukaratirwa S, Nkulungo E, Matenga E, Bhebhe E . Effect of host age in the distribution of adult Trichinella zimbabwensis in the small intestines of golden hamsters (Mesocricetus auratus) and Balb C mice. Onderstepoort J Vet Res. 2003; 70(2):169-73. View

18.

Klein M, Shearer J . Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application. J Diabetes Res. 2015; 2016:3898502. PMC: 4655283. DOI: 10.1155/2016/3898502. View

19.

Ranasinghe P, Jayawardena R, Chandrasena L, Noetzel V, Burd J . Effects of Lysulin™ supplementation on pre-diabetes: study protocol for a randomized controlled trial. Trials. 2019; 20(1):171. PMC: 6421713. DOI: 10.1186/s13063-019-3269-8. View

20.

Kalogeropoulou D, LaFave L, Schweim K, Gannon M, Nuttall F . Lysine ingestion markedly attenuates the glucose response to ingested glucose without a change in insulin response. Am J Clin Nutr. 2009; 90(2):314-20. DOI: 10.3945/ajcn.2008.27381. View