Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin
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 m...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Elsevier
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/112061/ |
| _version_ | 1848865845443297280 |
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| author | Zolkeflee, Nur Khaleeda Zulaikha Wong, Pei Lou Maulidiani, M. Ramli, Nurul Shazini Azlan, Azrina Mediani, Ahmed Tham, Chau Ling Abas, Faridah |
| author_facet | Zolkeflee, Nur Khaleeda Zulaikha Wong, Pei Lou Maulidiani, M. Ramli, Nurul Shazini Azlan, Azrina Mediani, Ahmed Tham, Chau Ling Abas, Faridah |
| author_sort | Zolkeflee, Nur Khaleeda Zulaikha |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T14:11:11Z |
| format | Article |
| id | upm-112061 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T14:11:11Z |
| publishDate | 2024 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1120612024-10-28T02:44:11Z http://psasir.upm.edu.my/id/eprint/112061/ Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin Zolkeflee, Nur Khaleeda Zulaikha Wong, Pei Lou Maulidiani, M. Ramli, Nurul Shazini Azlan, Azrina Mediani, Ahmed Tham, Chau Ling Abas, Faridah 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. Elsevier 2024 Article PeerReviewed 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 https://www.sciencedirect.com/science/article/abs/pii/S0006291X24003140?via%3Dihub 10.1016/j.bbrc.2024.149778 |
| spellingShingle | Zolkeflee, Nur Khaleeda Zulaikha Wong, Pei Lou Maulidiani, M. Ramli, Nurul Shazini Azlan, Azrina Mediani, Ahmed Tham, Chau Ling Abas, Faridah Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title | Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title_full | Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title_fullStr | Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title_full_unstemmed | Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title_short | Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| title_sort | revealing metabolic and biochemical variations via 1h nmr metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin |
| url | http://psasir.upm.edu.my/id/eprint/112061/ http://psasir.upm.edu.my/id/eprint/112061/ http://psasir.upm.edu.my/id/eprint/112061/ |