Next Article in Journal
CK2 Regulation: Perspectives in 2021
Next Article in Special Issue
Regulation of Insulin Clearance by Non-Esterified Fatty Acids
Previous Article in Journal
Genetics Is of the Essence to Face NAFLD
Previous Article in Special Issue
Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 9
Issue 10
10.3390/biomedicines9101360
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases

by
Natalie Youssef
1,2,
Mohamed Noureldein
1,2,
Rachel Njeim
1,2,
Hilda E. Ghadieh
1,2,
Frederic Harb
3,
Sami T. Azar
2,4,
Nassim Fares
5,* and
Assaad A. Eid
1,2,*
1
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Bliss Street, 11-0236, Riad El-Solh, Beirut 1107-2020, Lebanon
2
American University of Beirut (AUB) Diabetes, American University of Beirut, Bliss Street, 11-0236, Riad El-Solh, Beirut 1107-2020, Lebanon
3
Department of Life and Earth Sciences, Faculty of Sciences, Lebanese University, Fanar, Jdeidat P.O. Box 90656, Lebanon
4
Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Bliss Street, 11-0236, Riad El-Solh, Beirut 1107-2020, Lebanon
5
Laboratory of Physiology and Physiopathology, Faculty of Medicine, Saint Joseph University of Beirut, Damas Street, 11-5076, Riad El-Solh, Beirut 1107-2180, Lebanon
*
Authors to whom correspondence should be addressed.
Biomedicines 2021, 9(10), 1360; https://doi.org/10.3390/biomedicines9101360
Submission received: 13 July 2021 / Revised: 16 September 2021 / Accepted: 18 September 2021 / Published: 30 September 2021
(This article belongs to the Special Issue Role of Insulin Metabolism in Insulin Action and Metabolic Diseases)
Browse Figures
Versions Notes

Abstract

Diabetic kidney disease (DKD), a serious diabetic complication, results in podocyte loss and proteinuria through NADPH oxidases (NOX)-mediated ROS production. DUOX1 and 2 are NOX enzymes that require calcium for their activation which enters renal cells through the pivotal TRPC channels. Hypoglycemic drugs such as liraglutide can interfere with this deleterious mechanism imparting reno-protection. Herein, we aim to investigate the reno-protective effect of GLP1 receptor agonist (GLP1-RA), via its effect on TRPC6 and NADPH oxidases. To achieve our aim, control or STZ-induced T1DM Sprague–Dawley rats were used. Rats were treated with liraglutide, metformin, or their combination. Functional, histological, and molecular parameters of the kidneys were assessed. Our results show that treatment with liraglutide, metformin or their combination ameliorates DKD by rectifying renal function tests and protecting against fibrosis paralleled by restored mRNA levels of nephrin, DUOX1 and 2, and reduced ROS production. Treatment with liraglutide reduces TRPC6 expression, while metformin treatment shows no effect. Furthermore, TRPC6 was found to be directly interacting with nephrin, and indirectly interacting with DUOX1, DUOX2 and GLP1-R. Our findings suggest that treatment with liraglutide may prevent the progression of diabetic nephropathy by modulating the crosstalk between TRPC6 and NADPH oxidases.
Keywords: diabetic kidney disease; DUOX1/2; TRPC6; GLP-1; liraglutide diabetic kidney disease; DUOX1/2; TRPC6; GLP-1; liraglutide

Share and Cite

MDPI and ACS Style

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

AMA Style

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 Style

Youssef, 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

APA Style

Youssef, N., Noureldein, M., Njeim, R., Ghadieh, H. E., Harb, F., Azar, S. T., Fares, N., & Eid, A. A. (2021). Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases. Biomedicines, 9(10), 1360. https://doi.org/10.3390/biomedicines9101360

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop