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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 |
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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 |
Statistic Details: | View Download Statistic |
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