Upregulation of the renin angiotensin system (RAS) is involved in impaired insulin signaling and glucose intolerance in type 2 diabetes and burn injury. We showed that losartan, an AT1 receptor blocker, improved insulin signaling and glucose tolerance in burn‐injured rats. It has been shown that NF‐kappaB activation may play an important role in angiotensin II induced skeletal muscle insulin resistance. Our aim was to examine the possible mechanism of the cross talk between the RAS and insulin signaling systems in skeletal muscle in burn injury. To assess the involvement of NF‐kappaB, we measured the levels of IkappaB, an inhibitor of NF‐kappaB, in rectus abdominus muscle three days after sham or burn injury. A 30% body surface area burn was induced in male Sprague‐Dawley rats by immersion of the dorsum into 90C water for 15s. Losartan (30 mg/kg/day) or placebo (water) was given by gavage for three days post‐burn. The level of IkappaB decreased in burned rats given placebo but returned to sham placebo levels in burned rats given losartan. These data suggest that NF‐kappaB may be involved in the cross talk between the renin‐angiotensin system and insulin signaling in skeletal muscle in burn injured rats.
Insulin resistance after burn is associated with alterations in postreceptor insulin signaling and abnormal glucose homeostasis. We have previously shown that renin‐angiotensin system blockade using losartan, an AT1 receptor blocker, improves insulin signaling and glucose tolerance in burn injured rats. In this study, we examined the effects of losartan on 2‐deoxy‐glucose uptake into the soleus muscle of burned rats. A 30% body surface area burn was induced by immersion of the dorsum into 90ºC water for 15s. Sham burned rats were immersed in 23ºC water. Losartan (30 mg/kg/day) or placebo (water) was given by gavage for three days post‐burn resulting in sham burn (n= 8), burn placebo (n= 8) burn losartan (n= 8). Insulin (100 nM) stimulated glucose uptake was impaired in the soleus muscle of burn placebo animals as determined by 2‐deoxy‐glucose uptake, in vitro (77% decrease compared with sham). However, losartan treatment completely reversed this effect returning the uptake to the level of the sham burn animals. This suggests that the renin‐angiotensin system is involved in the insulin resistance of skeletal muscle that occurs in burn injury.
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