title: Blockade of the renin-angiotensin system improves insulin sensitivity in thermal injury.
abstract: Insulin resistance after burn is associated with alterations in postreceptor insulin signaling and abnormal glucose homeostasis. The renin-angiotensin system (RAS) exerts a largely inhibitory role on insulin action and is activated after burn injury. We hypothesized that upregulation of RAS is involved in the development of insulin resistance in burned rats. 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 water with a temperature level of 95 degrees C for 15 s. Sham-burned rats were immersed in water with a temperature level of 23 degrees C. Losartan (30 mg/kg per day) or placebo (water) was given by gavage immediately after the burn injury and daily for 3 days postburn injury, resulting in sham-burned, burn placebo, and burn losartan groups. Plasma angiotensin II levels between burn placebo and sham-burned groups were not different 3 days after burn injury. However, losartan significantly increased plasma angiotensin II levels (P < 0.05), suggesting blockade of the AT1 receptor. An oral glucose tolerance test was performed 3 days postburn injury. There was an increase in the area under the curve for insulin and the glucose insulin index in burn placebo group as compared with sham-burned group, indicating insulin resistance. Losartan treatment abolished the insulin resistance in burn as evidenced by an area under the curve for insulin and glucose insulin index lower than that in the burn placebo group and similar to that in the sham-burned group. This suggests that insulin resistance and glucose intolerance associated with burn injury is, in part, caused by RAS.
authors.affiliation: Division of Trauma and Critical Care, Department of Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
authors.forename: Sherry O
authors.initials: SO
authors.lastname: Kasper
authors.forename: Scott M
authors.initials: SM
authors.lastname: Castle
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Daley
authors.forename: Blaine L
authors.initials: BL
authors.lastname: Enderson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Karlstad
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D002056:Burns / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II; D019808:Losartan