Abstract
Introduction Not only is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it also increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. Aim The aim of the current study was the evaluation of the renoprotective effects of vitamin D in DN and the possible interplay between autophagy and mTOR pathways. Materials and Methods Fifty male Wistar albino rats were divided (10/group) into control, DN group, insulin-treated DN group, vitamin D-treated DN group, and combined insulin and vitamin D-treated DN group. Assessments of systolic blood pressure, albuminuria, creatinine clearance, serum glucose, insulin, urea, creatinine, inflammatory cytokines, oxidative stress markers, and rat kidney gene expression of mTOR were performed. Histopathological and immunohistochemical assessments of autophagy marker LC3 in rat kidneys were also performed. Results DN was associated with significant increases in SBP, urinary albumin, serum glucose, urea, creatinine, inflammatory cytokines, MDA, and mTOR gene expression (P < 0.05). However, there was significant decrease in creatinine clearance, serum insulin, GSH, and H score value of LC3 when compared with control group (P < 0.05). The combination of insulin and vitamin D treatment significantly restored DN changes when compared with the other treated groups, except in oxidative stress markers where there was an insignificant difference between the combination-treated and insulin-treated groups (P > 0.05). Conclusion It has been concluded that vitamin D is a potent adjuvant therapy in treatment of DN via downregulation of mTOR gene expression, stimulation of autophagy, and antioxidant, anti-inflammatory, and hypotensive effects.
Highlights
Is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients
Rats treated with insulin revealed significant decrease in serum glucose and increase in serum insulin when compared with DN group. ese results were in agreement with previous reported results [23]
Vitamin D-treated group revealed significant decrease in serum glucose and increase in serum insulin when compared with DN group. ese results were consistent with previous reported results [24]. e antidiabetic effect of vitamin D may be due to induction of insulin secretion by increasing intracellular calcium concentration and activation of β-cell calcium-dependent endopeptidase which facilitates the conversion of proinsulin to insulin [25]
Summary
Is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. Assessments of systolic blood pressure, albuminuria, creatinine clearance, serum glucose, insulin, urea, creatinine, inflammatory cytokines, oxidative stress markers, and rat kidney gene expression of mTOR were performed. DN was associated with significant increases in SBP, urinary albumin, serum glucose, urea, creatinine, inflammatory cytokines, MDA, and mTOR gene expression (P < 0.05). About 25–40% of diabetic patients develop DN within 20–25 years of the onset of their diabetes [1] It causes glomerular damage along with proteinuria and subsequent tubule-interstitial lesions, leading to end-stage renal disease [2]. A number of studies have reported that mTOR participates in the hyperproliferation of mesangial cells associated with DN [5]
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