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Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin


Citation

Zolkeflee, Nur Khaleeda Zulaikha and Wong, Pei Lou and Maulidiani, M. and Ramli, Nurul Shazini and Azlan, Azrina and Mediani, Ahmed and Tham, Chau Ling and Abas, Faridah (2024) Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin. Biochemical and Biophysical Research Communications, 708. art. no. 149778. ISSN 0006-291X

Abstract

The increasing prevalence of lean diabetes has prompted the generation of animal models that mimic metabolic disease in humans. This study aimed to determine the optimum streptozotocin-nicotinamide (STZ-NA) dosage ratio to elicit lean diabetic features in a rat model. It also used a proton nuclear magnetic resonance (1H NMR) urinary metabolomics approach to identify the metabolic effect of metformin treatment on this novel rat model. Three different STZ-NA dosage regimens (by body weight: Group A: 110 mg/kg NA and 45 mg/kg STZ; Group B: 180 mg/kg NA and 65 mg/kg STZ and Group C: 120 mg/kg NA and 60 mg/kg STZ) were administered to Sprague-Dawley rats along with oral metformin. Group A diabetic rats (A-DC) showed favorable serum biochemical analyses and a more positive response toward oral metformin administration relative to the other STZ-NA dosage ratio groups. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that glucose, citrate, pyruvate, hippurate, and methylnicotinamide differentiating the OPLS-DA of A-MTF rats (Group A diabetic rats treated with metformin) and A-DC model rats. Subsequent metabolic pathway analyses revealed that metformin treatment was associated with improvement in dysfunctions caused by STZ-NA induction, including carbohydrate metabolism, cofactor metabolism, and vitamin and amino acid metabolism. In conclusion, our results identify the best STZ-NA dosage ratio for a rat model to exhibit lean type 2 diabetic features with optimum sensitivity to metformin treatment. The data presented here could be informative to improve our understanding of non-obese diabetes in humans through the identification of possible activated metabolic pathways in the STZ-NA-induced diabetic rats model. © 2024 Elsevier Inc.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Food Science and Technology
Faculty of Medicine and Health Science
Institute of Bioscience
DOI Number: https://doi.org/10.1016/j.bbrc.2024.149778
Publisher: Elsevier
Keywords: H NMR urinary based metabolomics; Biochemical analyses; Metformin; Streptozotocin-nicotinamide induced diabetic rats; Type 2 diabetes mellitus
Depositing User: Ms. Azian Edawati Zakaria
Date Deposited: 28 Oct 2024 02:44
Last Modified: 28 Oct 2024 02:44
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.bbrc.2024.149778
URI: http://psasir.upm.edu.my/id/eprint/112061
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