PPAR-a is highly expressed in renal proximal tubules in which it influences metabolic activity (140). PPAR-a plays a role in lipid metabolism in renal cortex because its activation by clofibrates induces expression of 0-oxidation enzymes (141). Clinical evidence also suggests a beneficial effect of PPAR-a ligands on DN (142,143). In type 2 diabetic patients, treatment of dyslipidemia with gemfibrozil, one of antidyslipidemic agents and PPAR-a activators, stabilizes the increase in urinary albumin excretion
(143). In db/db type 2 diabetic mice, treatment with fenofibrate, another of PPAR-a activator, improves urinary albumin excretion rate and glomerular mesangial expansion
(144). One possible mechanism of PPAR-a action on the mesangial matrix production may be related to TGF-0 signaling (145). Clofibrate directly inhibits oxidant stress-induced TGF-0 expression in MCs (145). In addition, fenofibrate also downregulates TGF-0 and TGF-0 receptor type-2 expression decreasing type-IV collagen accumulation in diabetic glomeruli (144).
PPAR-0/5 is equally expressed in renal cortex and medulla as well as other tissues (48). However, the role of PPAR-0/5 in the kidney remains poorly understood. Overexpression of this isoform protects cultured medullary interstitial cells from hypertonicity-induced cell death, suggesting that PPAR-0/5 is an important survival factor for these cells exposed to the hypertonic environment of the renal medulla (146). Further studies are necessary to clarify the effect of PPAR-0/5 in kidney.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...