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

Copyright © 2024 Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:708

Enthalten in:

Biochemical and biophysical research communications - 708(2024) vom: 14. Apr., Seite 149778

Sprache:

Englisch

Beteiligte Personen:

Zolkeflee, Nur Khaleeda Zulaikha [VerfasserIn]
Wong, Pei Lou [VerfasserIn]
Maulidiani, M [VerfasserIn]
Ramli, Nurul Shazini [VerfasserIn]
Azlan, Azrina [VerfasserIn]
Mediani, Ahmed [VerfasserIn]
Tham, Chau Ling [VerfasserIn]
Abas, Faridah [VerfasserIn]

Links:

Volltext

Themen:

(1)H NMR urinary based metabolomics
25X51I8RD4
5W494URQ81
9100L32L2N
Biochemical analyses
Blood Glucose
Hypoglycemic Agents
Journal Article
Metformin
Niacinamide
Streptozocin
Streptozotocin-nicotinamide induced diabetic rats
Type 2 diabetes mellitus

Anmerkungen:

Date Completed 08.04.2024

Date Revised 08.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbrc.2024.149778

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369974506