A-046 Investigating the Role of RNase L in Metabolic Syndrome

Abstract

Abstract Background Metabolic syndrome is closely associated with the incidence of heart disease, type 2 diabetes, and stroke. Though the exact cause of metabolic syndrome is not known, many features of the metabolic syndrome are caused by insulin resistance. Recent years, accumulating evidence has shown that dysregulation of insulin signaling leads to insulin resistance. Interestingly, we have observed that RNase L affects the insulin signaling pathway by regulating the activation of insulin receptor subtrate-1 (IRS-1) in primary mouse embryonic fibroblasts (MEFs) and primary mouse hepatocyte. RNase L is an enzyme that plays a critical role in interferon function against viral infection and cellular proliferation. How RNase L affects the insulin signaling pathway is still unknown. Methods Age-matched C57BL/6 background RNase L wild type (WT) and knockout (KO) mice (n = 6–8) were fed on a chow diet. Metabolic tolerance tests including glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted on mice between 12 and 16 weeks old. Mice were subjected to either a morning (4 h) or an overnight (12 h) fast, then intraperitoneally injected with glucose (1.5 g/kg body weight) in PBS, pH 7.4, for GTT and insulin (1.0I U/kg body weight) for ITT. Blood was collected via tail vein at different time intervals over a span of 2 h and blood glucose was measured using a glucometer. Results We found that RNase L KO mice displayed significantly increased glucose tolerance in compared to RNase L WT mice as measured in the intraperitoneal glucose tolerance test. The glucose level in RNase L KO mice was 150% higher than that in RNase L WT mice after IP injection of glucose in 60 min. In the ITT experiment, the glucose level in RNase L KO mice was 130% higher than that in WT mice in 60 min post injection. Taken together, the results in GTT and ITT indicated that RNase L mediates the metabolism of glucose in vivo. Further investigation of molecular mechanisms is currently being conducted. Conclusion Our results suggests that RNase L plays a role in insulin sensitivity, which affects glucose metabolism.