Protective Actions of Anserine Under Diabetic Conditions

• Published in: International journal of molecular sciences Vol. 19; no. 9; p. 2751
• Main Authors: Peters, Verena, Calabrese, Vittorio, Forsberg, Elisabete, Volk, Nadine, Fleming, Thomas, Baelde, Hans, Weigand, Tim, Thiel, Christian, Trovato, Angela, Scuto, Maria, Modafferi, Sergio, Schmitt, Claus Peter
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-09-2018; MDPI
• Subjects: Amino acids; Animals; anserine; Anserine - therapeutic use; Antioxidants; Antioxidants - therapeutic use; Carbonyls; Carnosine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetic Nephropathies - drug therapy; Diabetic nephropathy; Drug dosages; Glucose; Heat shock proteins; Homeostasis; Hsp70; Hsp70 protein; Human behavior; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Immunoblotting; Intracellular; Intravenous administration; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Kidneys; Male; Measurement methods; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; mRNA; Nephropathy; Nitrates; Permeability; Polymerase chain reaction; Proteinuria; Rodents; Thioredoxin; vascular permeability; Germany; Hsp70; carnosine; proteinuria; anserine; vascular permeability; diabetes; diabetic nephropathy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092751

In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.
Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured.
Anserine has a higher antioxidant capacity compared to carnosine (
< 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all
< 0.05).
Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy.