Methylglyoxal (MG) Contributes to the Development of Insulin Resistance and Salt Sensitivity in Sprague Dawley (SD) Rats

Abstract

The present study was designed to investigate whether MG could induce insulin resistance and salt sensitivity in SD rats. Rats were given either 1% MG in tap drinking water or tap water alone. After 4‐week treatment insulin resistance was evaluated by glucose clamp technique. In another set of rats, either a high‐salt diet (HS; 4%) alone, standard rat chow with 1% MG in tap drinking water or HS plus MG was given for 4 weeks. Immunohistochemistry was performed to measure nitrotyrosine and MG‐induced advanced glycation endproducts (AGEs), Nƒ Ã‐carboxyethyl‐lysine (CEL) in the kidney. Systolic blood pressure (SBP) was measured by an tail‐cuff method. 4‐week treatment with 1% MG in drinking water significantly increased insulin resistance without altering the SBP. Co‐administration of MG and HS significantly increased SBP, urinary albumin excretion, urinary thiobarbituric acid‐reactive substances excretion and the renal nitrotyrosine expression in the kidney compared with MG or HS alone. Renal CEL was significantly increased in MG‐treated rats compared to non‐MG‐treated rats. These results indicate that MG induced insulin resistance and salt sensitivity at least in part by increasing oxidative stress and/or AGEs formation in SD rats. The present study provides further evidence for MG as one of the causative factors in the pathogenesis of insulin resistance and salt‐sensitive hypertension.