Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions
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Objective and design
Insulin resistant Otsuka–Long–Evans–Tokushima Fatty (OLETF) and its control Long–Evans Tokushima Ohtsuka (LETO) rats were used to generate a model for acute hyperuricemia. Upon the onset of insulin resistance OLETF rats were feed with high-purine diet, and the development of acute hyperuricemic renal injury and gouty-like lesions was monitored. Rosiglitazone was also administered to demonstrate whether improved insulin sensitivity would prevent high-purine diet induced renal injury and gouty-like lesions.
Otsuka–Long–Evans–Tokushima Fatty rats showed significant higher incidence of hyperuricemia as compared to the control LETO rats (77 vs. 36.1%, P < 0.05), indicating that insulin resistance exacerbates the development of hyperuricemia following high-purine load. Consistent with this observation, improvement of insulin sensitivity by administration of rosiglitazone significantly reduced high-purine diet induced renal injury and gouty-like lesions. It was found that insulin resistance is associated with impaired capability for maintaining the homeostasis of renal uric acid excretion and reabsorption. Upon high-purine load, insulin resistance enhances urate reabsorption as manifested by up-regulated URAT1 expression and reduces urate excretion as characterized by down-regulated UAT expression.
Our data demonstrated strong evidence indicating that insulin resistance acts as an independent risk factor predisposing OLETF rats more susceptible to the development of hyperuricemia and gouty arthritis following high-purine load.
KeywordsDiabetes Arthritis Adenosine
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