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Cited by 232Chronic Kidney Disease and DiabetesDiabetes Treatment and ManagementNitric Oxide and Endothelin Effects

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases

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Hendarto, Hari, Inoguchi, Toyoshi, Maeda, Yasutaka, Ikeda, Noriko, Zheng, Jing, Takei, Ryoko, Yokomizo, Hisashi, Hirata, Eiichi, Sonoda, Noriyuki, Takayanagi, Ryoichi·2012·Metabolism
DOI 10.1016/j.metabol.2012.03.002
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Abstract

Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular and renal diseases but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits oxidative stress and albuminuria in streptozotocin (STZ)-induced type 1 diabetes mellitus rats, via a protein kinase A (PKA)-mediated inhibition of renal NAD(P)H oxidases. Diabetic rats were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Oxidative stress markers (urinary 8-hydroxy-2'-deoxyguanosine and renal dihydroethidium staining), expression of renal NAD(P)H oxidase components, transforming growth factor-β (TGF-β), fibronectin and urinary albumin excretion were measured. In vitro effect of liraglutide was evaluated using cultured renal mesangial cells. Administration of liraglutide did not affect plasma glucose levels or body weights in STZ diabetic rats, but normalized oxidative stress markers, expression of NAD(P)H oxidase components, TGF-β, fibronectin in renal tissues and urinary albumin excretion, all of which were significantly increased in diabetic rats. In addition, in cultured renal mesangial cells, incubation with liraglutide for 48 h inhibited NAD(P)H-dependent superoxide production evaluated by lucigenin chemiluminescence in a dose-dependent manner. This effect was reversed by both PKA inhibitor H89 and adenylate cyclase inhibitor SQ22536, but not by Epac2 inhibition via its small interfering RNA. Liraglutide may have a direct beneficial effect on oxidative stress and diabetic nephropathy via a PKA-mediated inhibition of renal NAD(P)H oxidase, independently of a glucose-lowering effect.

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Metadata

Authors
Hendarto, H., Inoguchi, T., Maeda, Y., Ikeda, N., Zheng, J., Takei, R., Yokomizo, H., Hirata, E., Sonoda, N., & Takayanagi, R.
Affiliations
Kyushu University (JP)
Corresponding author
Inoguchi, Toyoshi
ORCID
Venue
Metabolism
Publisher
Elsevier BV
Published
2012-10
Volume
61
Issue
10
Pages
1422-1434
ISSN
0026-0495 (ISSN-L)
DOI
10.1016/j.metabol.2012.03.002
OpenAlex
W1983883248
Cited by
232
References
43
Citations by year
2026: 7 · 2025: 17 · 2024: 20 · 2023: 16 · 2022: 8 · 2021: 17 · 2020: 21 · 2019: 21 · 2018: 18 · 2017: 15 · 2016: 16 · 2015: 19 · 2014: 14 · 2013: 18 · 2012: 4
FWCI
13.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Universitas Islam Negeri Syarif Hidayatullah Institutional Repository (Universitas Islam Negeri Syarif Hidayatullah Jakarta) (submittedVersion, cc-by-nc)
Funders
Japan Society for the Promotion of Science (23390247)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords
liraglutide, GLP-1 analogues, diabetic nephropathy, oxidative stress, albuminuria, protein kinase A, NADPH oxidase, type 1 diabetes, streptozotocin-induced diabetes, renal mesangial cells, superoxide production, TGF-beta, fibronectin, Epac2, renal fibrosis
MeSH terms
Liraglutide, Adenine, Albuminuria, Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Humans, Isoquinolines, Kidney, Male, Multienzyme Complexes, NADH, NADPH Oxidoreductases, Streptozocin, Sulfonamides, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases, Oxidative Stress, Rats, Glucagon-Like Peptide 1

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