Cross-talk between inflammatory and insulin signaling may contribute to insulin resistance induced by low salt intake: Effect of losartan on JNK activity and Akt phosphorylation

It is known that low salt diet (LS) impairs insulin (INS) signaling in liver (L) and muscle (M) and increases plasma angiotensin II (AII) which may enhance JNK activity. Objective: To evaluate if losartan (LOS) improves INS sensitivity by decreasing JNK activity and phosphorylation (PHOS) of IRS-1ser307 in tissues. Methods: Twelve-week-old rats were fed a LS (0.15% NaCl, n=8) or normal salt diet (NS: 1.3%, n=8) since weaning. Four groups were studied: LS+LOS (30mg/kg/day), LS+vehicle, NS+LOS and NS+vehicle during 1 week. Plasma glucose (GLU) and INS, plasma and tissue AII and HOMA index were evaluated. Akt PHOS after INS stimulation, activation of JNK, and IRS-1ser307 PHOS (immunoblotting) were determined in the L, M and white adipose tissue (WAT). Results (mean ± SEM – P<0.05): GLU, INS and HOMA were higher on LS than on NS (INS: LS 712 ± 6, NS 257 ± 4 pmol/l). Plasma, L and M AII were higher and WAT AII was lower on LS (52 ± 25) than on NS (103 ± 28 ng/g). Compared to LS, there was an 80% increase in Ak...