Vitamin C is essential for the renal function maintenance in diabetes. - GreenMedInfo Summary
Vitamin C deficiency exacerbates diabetic glomerular injury through activation of transforming growth factor-β signaling.
Biochim Biophys Acta. 2017 09 ;1861(9):2186-2195. Epub 2017 Jun 23. PMID: 28652077
BACKGROUND: The hyperglycemia and hyperoxidation that characterize diabetes lead to reduced vitamin C (VC) in diabetic humans and experimentally diabetic animals. Herein, we access the effects of VC deficiency on the diabetic kidney injury and explore the underlying mechanism.
METHODS: l-gulonolactone oxidase conventional knockout (Gulo-/-) mice genetically unable to synthesize VC were subjected to streptozotocin-induced diabetic kidney injury and the role of VC deficiency was evaluated by biochemical and histological approaches. Rat mesangial cells were cultured to investigate the underlying mechanism.
RESULTS: Functionally, VC deficiency aggravates the streptozotocin-induced renal insufficiency, exhibiting the increased urine albumin, water intake, and urine volume in Gulo-/- mice. Morphologically, VC deficiency exacerbates the streptozotocin-induced kidney injury, exhibiting the increased glomerular expansion, deposition of Periodic Acid-Schiff- and Masson-positive materials, and expression ofα-smooth muscle actin, fibronectin and type 4 collagen in glomeruli of Gulo-/- mice. Mechanistically, VC activates protein kinase B (Akt) to destabilize Ski and thereby induce the expression of Smad7, resulting in suppression of TGF-β/Smad signaling and extracellular matrix deposition in mesangialcells.
CONCLUSIONS: VC is essential for the renal function maintenance in diabetes.
GENERAL SIGNIFICANCE: Compensation for the loss of VC could be an effective remedy for diabetic kidney injury.