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[Intervention effects of oral active AdipoRon on liver oxidative stress in type 2 diabetic mice]
Min Xiao1, Xiao-Hu Qu1, Hui Chen1
1Department of Biology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
Objective:
To explore the intervention effects of oral active AdipoRon on liver oxidative stress in type 2 diabetic mice, which provides basic data for clinical application.
Methods:
Thirty-two healthy male C57BL/6 mice were divided into 4 groups:normal group (NC, n=8), diabetes mellitus group (DM, n=8), high dose AdipoRon treatment group (DM + H, n=8) and low dose AdipoRon treatment group (DM + L, n=8). Following six weeks high fat feed, mice of DM, DM + H and DM + L were intraperitoneally injected with 40 mg/kg streptozocin (STZ), leading to type 2 diabetes. Afterwards, DM + H group and DM + L group were continuously treated with high dose and low doses of oral AdipoRon respectively for 10 days, following which, related biochemical indicators were detected. Western blot method was used to detect the p-IRS-1 protein expression in liver tissue and RT-PCR method to detect PDX-1 mRNA expression in the pancreas.
Results:
The blood glucose of DM group was obviously higher than that of NC group (P < 0.05). Compared to that of DM group, blood glucose of DM + H group as well as DM + L group was significantly lower. Activity of superoxide dismutase (SOD), catalase (CAT) in liver tissue of DM mice was significantly lower than that of NC group (P < 0.05); activity of malondialdehyde (MDA) and nitric oxide synthase (NOS) in DM group significantly higher than that of NC group (P < 0.05); activity of SOD and CAT in DM + L group and DM + H group obviously higher than DM group (P < 0.05); activity of MDA and NOS in DM + L group and DM + H group significantly lower than DM group (P < 0.05). And the p-IRS-1 protein expression in liver tissue and PDX-1 mRNA level in pancreas increased significantly (P < 0.05).
Conclusions:
Oral active Adi-poRon which reduced the blood glucose levels of mice had a certain intervention effect on liver tissue oxidative stress in type 2 diabetes mice.
Insights
Oral AdipoRon effectively reduced blood glucose and liver oxidative stress in type 2 diabetic mice. This study provides foundational data for AdipoRon
Area of Science:
- Biochemistry and Molecular Biology
- Endocrinology and Metabolism
- Pharmacology
Background:
- Type 2 diabetes mellitus is characterized by hyperglycemia and oxidative stress.
- Liver oxidative stress plays a critical role in the pathogenesis of type 2 diabetes complications.
- AdipoRon is an oral active compound with potential therapeutic benefits.
Purpose of the Study:
- To investigate the effects of oral AdipoRon on liver oxidative stress in a mouse model of type 2 diabetes.
- To evaluate AdipoRon's impact on key biochemical markers and gene/protein expression related to diabetes and oxidative stress.
- To provide preclinical data supporting the potential clinical application of AdipoRon for type 2 diabetes.
Main Methods:
- Type 2 diabetes was induced in male C57BL/6 mice using streptozotocin (STZ) after high-fat diet feeding.
- Mice were divided into normal control, diabetes mellitus, and two AdipoRon treatment groups (high and low dose).
- Blood glucose, liver oxidative stress markers (SOD, CAT, MDA, NOS), liver p-IRS-1 protein, and pancreatic PDX-1 mRNA were assessed.
Main Results:
- AdipoRon treatment significantly reduced blood glucose levels in diabetic mice compared to untreated controls.
- AdipoRon administration increased the activity of antioxidant enzymes (SOD, CAT) and decreased lipid peroxidation markers (MDA, NOS) in the liver.
- AdipoRon treatment led to increased liver p-IRS-1 protein expression and pancreatic PDX-1 mRNA levels.
Conclusions:
- Oral AdipoRon demonstrates significant intervention effects on liver oxidative stress in type 2 diabetic mice.
- AdipoRon effectively lowers blood glucose levels and ameliorates oxidative damage in the liver.
- These findings suggest AdipoRon as a promising therapeutic agent for managing type 2 diabetes.
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