Insulin resistance induced by low salt diet is linked with RAS activity, oxidative stress and beta‐cell dysfunction in adult rats

We recently showed that low salt diet (LS) induces insulin (INS) resistance, impairs INS signaling, and increases angiotensin II (AII) in several tissues with important function in the control of INS action in rats. AII and others components of the RAS have been identified in pancreatic islets and AII can interfere in the control of INS release and increases oxidative stress (OS). Objective To evaluate the effects of LS and losartan (LOS) on RAS activity, beta‐cell function and NAD(P)H activation (NAD) in isolated pancreatic islets from rats with INS resistance. Methods Rats were fed a LS (0.15% NaCl) or normal‐salt diet (NS: 1.3%) since weaning. At 12 wk of age, they received LOS. Blood glucose (G), plasma INS, and HOMA were evaluated. Protein expression of p47 PHOX and gp91 PHOX , AII, AII type 1 receptor (AT 1 R) gene and protein expression, and binding of an AT 1 R conformation‐specific antibody were assessed in pancreatic islets. The pools of islets were incubated in 2 different G concentrations (2.8 and 16.7mM) and beta‐cell function was evaluated by dynamic INS secretion. Results (P<0.05, n=4) INS, HOMA, AII, NAD, and AT 1 R protein were greater in LS (gp91: 1352±112.6) than in NS (gp91: 1220±102.2 AU). G and NAD were lower in LS+LOS (gp91: 976.5±46.51 AU) than in LS. Finally, INS release from the islets was similar in LS and in NS on a basal G concentration, but was lower in LS and was higher in LS+LOS islets when exposed to16.7mM G. Conclusions LS increases RAS activity and OS in islets and can lead to beta‐cell dysfunction. In LS, LOS improved glucose‐induced INS release and reduced OS. These effects may involve AT 1 R and AII may be a pathway that connects INS resistance and beta‐cell dysfunction in LS. Supported by FAPESP