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To examine if peroxiredoxin 2 (Prx2) deficiency aggravates high-fat diet-induced insulin resistance. Insulin sensitivity was measured in Prx2 knockout (KO) and wild-type (WT) littermates using the hyperinsulinemic-euglycemic clamp. Whole body glucose turnover, glucose uptake, and levels of glucose transporter 4 (Glut4) protein in the skeletal muscle were found to be lower. This was followed by increased expression of oxidative stress markers in Prx2 KO mice than that in WT mice in the control diet group. Although, a 12-week high-fat diet induced insulin resistance and enhanced oxidative stress in both genotypes, there was no difference between WT and Prx2 KO mice with respect to insulin sensitivity and the level of oxidative stress markers. Accordingly, the levels of phosphorylated Akt and Glut4 were similar between the two genotypes. These results suggest that Prx2 does not affect high-fat diet-induced oxidative stress and insulin resistance in mice. [ABSTRACT FROM AUTHOR]

This study examined the role of peroxiredoxin2 (Prx2) in aging-induced insulin resistance and reduction in skeletal muscle function in young (2-month-old) and old (24-month-old) Prx2 knockout (KO) and wild-type mice. Plasma insulin levels increased with aging in Prx2 KO mice but not in wild-type mice. Insulin sensitivity in the whole-body and skeletal muscle as assessed with the hyperinsulinemic-euglycemic clamp was lower in Prx2 KO mice than in wild-type mice in the old group but was not significantly different between the two genotypes in the young group. Insulin-induced activation of intracellular signaling molecules was also suppressed in old Prx2 KO mice compared to their wild-type littermates. Oxidative stress, inflammation, and p53 expression levels in skeletal muscle were higher in Prx2 KO mice than in wild-type mice in the old group but were not different between the two genotypes in the young group. p53 expression was negatively correlated with skeletal muscle insulin sensitivity in old mice. Skeletal muscle mass was similar between the two genotypes but grip strength was reduced in old Prx2 KO mice compared to old wild-type mice. These results suggest that Prx2 plays a protective role in aging-induced insulin resistance and declines in muscle strength by suppressing oxidative stress. [ABSTRACT FROM AUTHOR]

Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice. [ABSTRACT FROM AUTHOR]