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

Abstract

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 Akt PHOS, 90% and 87% decrease in JNK activation and in IRS-1ser307 PHOS, respectively, in the L of LS+LOS. Similar results were observed in the M. There were no differences in Akt, JNK and IRS-1ser307 PHOS in the WAT among groups. Akt, JNK and IRS-1ser307 PHOS were similar among the LS+LOS and NS. Conclusions INS resistance induced by LS is tissue-specific and is associated with activation of JNK and IRS-1ser307 PHOS. AII levels are increased by LS in the tissues in which there is impaired INS signaling and increased JNK activity and LOS improved INS sensitivity in LS. Supported by FAPESP