Liraglutide treatment attenuates inflammation markers in the cardiac, cerebral and renal microvasculature in streptozotocin‐induced diabetic rats

• Published in: European journal of clinical investigation Vol. 52; no. 9; pp. e13807 - n/a
• Main Authors: Baylan, Umit, Korn, Amber, Emmens, Reindert W., Schalkwijk, Casper G., Niessen, Hans W. M., Krijnen, Paul A. J., Simsek, Suat
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2022
• Subjects: advanced glycation endproducts; Atria; Blood vessels; Carboxymethyllysine; Cell adhesion molecules; Cerebellum; cerebral vasculature; Cerebrum; CML; CYBB protein; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Endothelial cells; GLP‐1 analogue; Glucagon; Glucose; Glycosylation; ICAM‐1 (CD54); Inflammation; Injection; intramyocardial vasculature; Kidneys; Liraglutide; Lysine; Microvasculature; NADPH oxidases; NOX4 protein; Oxidative stress; renal vasculature; Rodents; Streptozocin; VCAM‐1 (CD106); CML; NADPH oxidases; VCAM-1 (CD106); GLP-1 analogue; renal vasculature; ICAM-1 (CD54); diabetes mellitus; intramyocardial vasculature; advanced glycation endproducts; Liraglutide; cerebral vasculature
• ISSN: 0014-2972; 1365-2362; 1365-2362
• DOI: 10.1111/eci.13807

Background Diabetes mellitus (DM) induces cardiac and cerebral microvascular dysfunction via increased glycation, oxidative stress and endothelial activation. Liraglutide, a glucagon‐like peptide‐1 analogue, inhibited NOX2 and adhesion molecules in isolated endothelial cells. Here, we have studied how Liraglutide affects advanced glycation, NOX expression and inflammation of the cardiac, cerebral and renal microvasculature in diabetic rats. Methods DM was induced in Sprague–Dawley rats (n = 15) via intraperitoneal streptozotocin (STZ) injection (60 mg/kg bodyweight). Ten control rats remained nondiabetic. From day 9 post‐STZ injection, Liraglutide (200 μg/kg bodyweight; n = 7) or vehicle (n = 8) was injected subcutaneously daily until termination on day 29. The advanced glycation endproduct N‐ε‐(carboxymethyl)lysine (CML), NOX2, NOX4, ICAM‐1 and VCAM‐1 were subsequently immunohistochemically analysed and quantified to compare Liraglutide treatment with placebo. Results In the heart, Liraglutide treatment significantly reduced the DM‐increased scores/cm2 for CML in both ventricles (from 253 ± 53 to 72 ± 12; p = .003) and atria (343 ± 29 to 122 ± 8; p = .0001) and for NOX2, ICAM‐1 and VCAM‐1, but not for NOX4. Also in the cerebrum and cerebellum of the brain, Liraglutide significantly reduced the scores/cm2 for CML (to 60 ± 7 (p = .0005) and 47 ± 13 (p = .02), respectively), and for NOX2 and NOX4. In the kidney, the DM‐induced expression of ICAM‐1 and VCAM‐1 was decreased in the blood vessels and glomeruli by Liraglutide treatment. Liraglutide did not affect blood glucose levels or bodyweight. Conclusions Our study implies that Liraglutide protects the cardiac, cerebral and renal microvasculature against diabetes‐induced dysfunction, independent of lowering blood glucose in a type 1 diabetes rat model.