Blockade Of The Renin-Angiotensin System Suggests P38 As A Cross-Talk Mechanism Between The Renin-Angiotensin System And The Insulin Signaling Pathway

Burn injury has been associated with insulin resistance. We have shown that losartan, an AT1 receptor blocker within the renin-angiotensin system (RAS), induces modifications in the intracellular insulin signaling pathway. We propose that phosphorylation of p38, a mitogen-activated protein kinase (MAPK) in the RAS pathway, is an agent in the cross talk mechanism between RAS and the insulin receptor pathway. Male Sprague Dawley rats were placed in 90°C water for 15 seconds resulting in a 30% total body surface are burn; sham rats were immersed in 23°C water. Losartan (30mg/kg/day) was administered for three consecutive days postburn by gavage. Using rectus abdominus muscle, phosphorylated p38 levels were examined by Western blot analysis. Rats treated with losartan showed a significant increase in phospho-p38 (p<0.05, n=6) as compared with sham rats treated with a placebo (water). The increase in phospho-p38 parallels our previous findings that show an increase in plasma membrane GLUT4 transporter and IRS-1 associated PI3-kinase in the insulin signaling pathway. These correlations support a role for p38 as a cross talk mechanism between RAS and insulin signaling.