Blockade of the Renin‐Angiotensin System Increases Skeletal Muscle Total IRS‐1 in Burn Injury

We have shown a correlation between burn injury and insulin resistance as a result of modification of the insulin receptor pathway. More specifically, the effects of total IRS‐1 were studied by inhibiting the renin‐angiotensin (RAS) with losartan, an AT 1 receptor blocker. Male Sprague Dawley rats were subjected to a 30% total body surface area burn in 90°C water for 15 seconds while sham rats were immersed in 23°C water. Losartan (30 mg/kg/day) was administered by gavage three days consecutively post‐burn. Total IRS‐1 was determined in rectus abdominus muscle by Western blotting. There was a significant increase in total IRS‐1 (p<0.05, n=7) in muscle from burned rats treated with losartan as compared with sham and burned rats treated with placebo (water). We have observed a similar pattern later in the pathway among the plasma membrane GLUT4 transporter and IRS‐1 associated PI3‐kinase levels. These findings show a significant increase in total IRS‐1 as a result of losartan treatment and suggests a potential role of RAS in regulating total IRS‐1 in skeletal muscle.