Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes

Autor: Shingo Nishishita, Tetsuharu Takatsuka, Nobuo Kajitani, Kenichi Shikata, Hitomi Kataoka, Motofumi Sasaki, Satoshi Miyamoto, Ryo Kodera, Chikage Sato, Hirofumi Makino, Kei Sarai, Daisho Hirota, Daisuke Ogawa
Rok vydání: 2011
Předmět:
Blood Glucose
Collagen Type IV
Male
Agonist
endocrine system
medicine.medical_specialty
medicine.drug_class
Endocrinology
Diabetes and Metabolism
Blotting
Western
Fluorescent Antibody Technique
Glucagon-Like Peptide-1 Receptor
Cell Line
Rats
Sprague-Dawley
Diabetic nephropathy
Cell Line
Tumor
Internal medicine
Diabetes mellitus
Receptors
Glucagon
Internal Medicine
Animals
Humans
Medicine
Diabetic Nephropathies
Receptor
Glucagon-like peptide 1 receptor
Kidney
Type 1 diabetes
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Venoms
business.industry
digestive
oral
and skin physiology
NF-kappa B
Intercellular Adhesion Molecule-1
medicine.disease
Rats
Diabetes Mellitus
Type 1
medicine.anatomical_structure
Endocrinology
Exenatide
Peptides
business
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Zdroj: Diabetologia. 54:965-978
ISSN: 1432-0428
0012-186X
DOI: 10.1007/s00125-010-2028-x
Popis: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose.We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro.Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells.These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.
Databáze: OpenAIRE
Externí odkaz: