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

被引:0
作者
Zolkeflee, Nur Khaleeda Zulaikha [1 ]
Wong, Pei Lou [2 ]
Maulidiani, M. [3 ]
Ramli, Nurul Shazini [2 ]
Azlan, Azrina [4 ]
Mediani, Ahmed [5 ]
Tham, Chau Ling [6 ]
Abas, Faridah [1 ,2 ]
机构
[1] Univ Putra Malaysia, Inst Biosci, Nat Med & Prod Res Lab, Serdang, Selangor, Malaysia
[2] Univ Putra Malaysia, Fac Food Sci & Technol, Dept Food Sci, Serdang, Selangor, Malaysia
[3] Univ Malaysia Terengganu, Sch Fundamental Sci, Kuala Nerus, Terengganu, Malaysia
[4] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Nutr & Dietet, Serdang, Selangor, Malaysia
[5] Univ Kebangsaan Malaysia, Inst Syst Biol INBIOSIS, Metabol Res Lab, Bangi, Malaysia
[6] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang, Selangor, Malaysia
关键词
Type 2 diabetes mellitus; Metformin; Streptozotocin-nicotinamide induced diabetic; rats; 1 H NMR urinary based metabolomics; Biochemical analyses; ANIMAL-MODELS; PREVALENCE; SECRETION; DIET;
D O I
10.1016/j.bbrc.2024.149778
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 ( 1 H 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.
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页数:15
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