Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Studies
2.2. Sacrifice and Organ Harvesting
2.3. Blood–Urine Biochemical Analysis
2.4. mRNA Extraction and cDNA Synthesis
2.5. Real-Time PCR
2.6. Periodic Acid-Schiff (PAS) and Masson’s Trichrome (MT) Staining
2.7. AMPK Activity Assay
2.8. Immunohistochemistry for TRPC6
2.9. Western Blot
2.10. Detection of Intracellular Superoxide in Kidney Cortex Using HPLC
2.11. NADPH Oxidase Activity Analysis
2.12. Protein Interactions and Pathway Analysis
2.13. Statistical Analysis
3. Results
3.1. Metabolic Parameters
3.2. Liraglutide, Metformin or Their Combination Reverse Renal Dysfunction Observed in T1DM Rats
3.3. Treatment with Pharmacological Doses of Liraglutide, Metformin or Their Combination Reversed T1DM-Induced Alteration in Their Respective Signaling Targets
3.4. DUOX1 and DUOX2 of the NADPH Family of Enzymes Play a Role in T1DM-Induced ROS Production
3.5. GLP-1R but Not AMPK Regulate TRPC6 Expression in T1DM Rats
3.6. TRPC6 Interacts with DUOX1, DUOX2 and GLP-1R in Humans
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Youssef, N.; Noureldein, M.; Njeim, R.; Ghadieh, H.E.; Harb, F.; Azar, S.T.; Fares, N.; Eid, A.A. Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases. Biomedicines 2021, 9, 1360. https://doi.org/10.3390/biomedicines9101360
Youssef N, Noureldein M, Njeim R, Ghadieh HE, Harb F, Azar ST, Fares N, Eid AA. Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases. Biomedicines. 2021; 9(10):1360. https://doi.org/10.3390/biomedicines9101360
Chicago/Turabian StyleYoussef, Natalie, Mohamed Noureldein, Rachel Njeim, Hilda E. Ghadieh, Frederic Harb, Sami T. Azar, Nassim Fares, and Assaad A. Eid. 2021. "Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases" Biomedicines 9, no. 10: 1360. https://doi.org/10.3390/biomedicines9101360