Abstract
BackgroundCarbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders. The present study tested the influence of carbohydrate-energy restricted diet (CR) on type-1 diabetes induced renal dysfunction, hypoxia and structural alterations against diabetic rat group fed control diet (ad libitium).MethodsMale wistar rats weighing between 180 and 190 g were subjected to 30% carbohydrate energy restricted diet (CR) and diabetes was induced by administration of streptozotocin (45 mg/kg., i.p). Assessment of renal function was done after 4 weeks by determining the serum levels of creatinine, BUN, proteinuria. Oxidative stress was determined by estimating the reduced glutathione, malonaldehyde levels, catalase activity and extent of renal hypoxia by estimating the HIF-1α levels in kidney tissue homogenates. Histological studies were conducted on kidney sections using hematoxylin and eosin, periodic acid-schiff staining.ResultsDiabetic rats exhibited marked hyperglycemia and renal dysfunction developed in diabetic rats fed control diet (ad libitium) as shown by significantly elevated levels of serum creatinine, BUN and massive proteinuria after 4 weeks period. CR diet treatment in diabetic rats significantly lowered hyperglycemia, reversed the above renal functional abnormalities, reduced oxidative stress and enhanced HIF-1α levels. Furthermore histological examination of kidney sections from CR diet treated diabetic rat group showed absence of glomerular hypertrophy, mesangial expansion and tubular vacoulations.ConclusionOur results demonstrated that CR diet treatment in diabetic rats attenuated renal damage by reducing oxidative stress and preventing the development of hypoxia by up-regulating HIF-1α levels.
Highlights
Carbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders
During oxygen deprivation in hypoxic sate Hypoxia inducible factor-1 alpha (HIF-1α) accumulation occurs which combines with β subunit to form transcriptionally active heterodimer that subsequently remodels the renal hemodynamics by producing blood cells and by inducing formation of new vessels via targeting erythropoietin and vascular endothelium growth factor (VEGF) [7, 8]
During second week diabetic control group showed a significant decline of body weight 32.86% and 33.50% (p < 0.001) compared
Summary
Carbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders. The present study tested the influence of carbohydrate-energy restricted diet (CR) on type-1 diabetes induced renal dysfunction, hypoxia and structural alterations against diabetic rat group fed control diet (ad libitium). HIFs modulate key metabolic pathways to optimize glucose and O2 utilization for generation of sufficient amounts of ATP. It is comprised of two different subunits: an α-subunit that is rapidly deteriorated by prolyl hydroxylases in the presence of oxygen and a constitutively expressed β-subunit. In addition a study has demonstrated that pharmacological activation of HIFs by cobalt treatment prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, kidney function and reduced proteinuria and tubulointerstitial damage [9]
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