Thermal injury induced insulin resistance is associated with the renin‐angiotensin system (RAS)

Abstract

Insulin resistance after burn is associated with alterations in postreceptor insulin signaling and abnormal glucose homeostasis. RAS exerts a largely inhibitory role on insulin action and is activated after burn injury. We examined the possibility that an angiotensin II type-1 (AT1) receptor blocker, losartan, enhances insulin sensitivity and thereby increases glucose tolerance in thermally injured rats. A 30% body surface area burn was induced by immersion of the dorsum into 90°C water for 15s. Sham burned rats were immersed in 23°C water. Losartan (30 mg/kg/day) or placebo (water) was given by gavage for three days post-burn resulting in sham burn, burn placebo, burn losartan. Plasma angiotensin II levels between burn and sham burn were not different three days post-burn. However, losartan significantly increased plasma angiotensin II levels (p<0.05), suggesting blockade of the AT1 receptor. The oral glucose tolerance test (Table) showed an increase in the area under the curve (AUC) for insulin and the glucose insulin (GI) index in burn placebo as compared with sham burn, indicating insulin resistance. Losartan treatment abolished the insulin resistance in burn as evidenced by an AUC for insulin and GI index lower than burn placebo and similar to sham burn. This suggests that insulin resistance and glucose intolerance associated with burn injury is due, in part, to RAS.