l-Homoarginine supplementation prevents diabetic kidney damage.
Michael D WetzelTing GaoManjeri VenkatachalamSidney M MorrisAlaa S AwadPublished in: Physiological reports (2020)
l-homoarginine is an endogenous, non-proteinogenic amino acid that has emerged as a new player in health and disease. Specifically, low l-homoarginine levels are associated with cardiovascular diseases, stroke, and reduced kidney function. However, the role of l-homoarginine in the pathogenesis of diabetic nephropathy (DN) is not known. Experiments were conducted in 6-week-old Ins2Akita mice supplemented with l-homoarginine via drinking water or mini osmotic pump for 12 weeks. Both plasma and kidney l-homoarginine levels were significantly reduced in diabetic mice compared to nondiabetic controls. Untreated Ins2Akita mice showed significant increases in urinary albumin excretion, histological changes, glomerular macrophage recruitment, the inflammatory cytokine KC-GRO/CXCL1, and urinary thiobarbituric acid reactive substances (TBARS) excretion as an indicator of oxidative stress, along with a significant reduction in kidney nitrate + nitrite levels compared to control mice at 18 weeks of age. In contrast, l-homoarginine supplementation for 12 weeks in Ins2Akita mice, via either drinking water or mini osmotic pump, significantly reduced albuminuria, renal histological changes, glomerular macrophage recruitment, KC-GRO/CXCL1 levels, urinary TBARS excretion, and largely restored kidney nitrate + nitrite levels. These data demonstrate that l-homoarginine supplementation attenuates specific features of DN in mice and could be a potential new therapeutic tool for treating diabetic patients.
Keyphrases
- drinking water
- oxidative stress
- diabetic nephropathy
- high fat diet induced
- health risk
- nitric oxide
- health risk assessment
- adipose tissue
- cardiovascular disease
- healthcare
- type diabetes
- dna damage
- amino acid
- magnetic resonance
- mental health
- atrial fibrillation
- computed tomography
- metabolic syndrome
- magnetic resonance imaging
- randomized controlled trial
- risk assessment
- wild type
- electronic health record
- signaling pathway
- social media
- endoplasmic reticulum stress
- subarachnoid hemorrhage
- diabetic rats
- endothelial cells