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Indapamide Increases IRS1 Expression and Modifies Adiponectin/NLRP3/PPARγ Crosstalk in Type 2 Diabetic Rats
Mahmoud M Samaha1, Manar G Helal1, Mohamed El-Sherbiny2,3
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Antioxidants (Basel, Switzerland)
|April 23, 2022
Summary
Indapamide demonstrates significant anti-diabetic, antioxidant, and anti-inflammatory effects comparable to canagliflozin in type 2 diabetes. This study highlights indapamide
Area of Science:
- Endocrinology
- Pharmacology
- Metabolic Diseases
Background:
- Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, impaired insulin secretion, and altered adipokine profiles.
- Oxidative stress and inflammation are key contributors to T2DM pathogenesis.
- Adiponectin plays a crucial role in metabolic regulation, and its modulation is a therapeutic target.
Purpose of the Study:
- To evaluate the anti-diabetic efficacy of canagliflozin (CANA) and indapamide (INDA) in a T2DM model.
- To investigate their roles as adiponectin modulators.
- To assess their impact on oxidative stress, inflammation, and related signaling pathways.
Main Methods:
- Experimentally induced type 2 diabetes mellitus in a suitable animal model.
- Administration of canagliflozin and indapamide.
- Assessment of glycemic control (blood glucose, HbA1c), insulin and adiponectin levels.
- Measurement of oxidative stress markers (MDA, TAC) and antioxidant gene expression (Nrf2).
- Evaluation of inflammatory markers (TNF-α, IL-10, NLRP3, NF-κB, CD68) and key metabolic signaling proteins (PPARγ, IRS1).
Main Results:
- T2DM induced hyperglycemia, reduced insulin and adiponectin, increased oxidative stress (MDA) and inflammation (TNF-α, NLRP3, NF-κB, CD68), and altered gene expressions (Nrf2, PPARγ, IRS1).
- Both CANA and INDA treatments improved glycemic control, increased adiponectin and insulin, reduced oxidative stress and inflammation.
- INDA showed comparable or superior effects to CANA in improving HbA1c, IRS1 expression, and reducing NF-κB and CD68.
- INDA modulated adiponectin/NLRP3/PPARγ crosstalk, suggesting a multifaceted therapeutic mechanism.
Conclusions:
- Indapamide exhibits significant anti-diabetic, antioxidant, and anti-inflammatory properties in experimental T2DM.
- Indapamide's therapeutic effects are comparable, and in some aspects superior, to canagliflozin.
- Indapamide represents a potential therapeutic agent for T2DM, acting through modulation of adiponectin signaling and inflammatory pathways.
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