Table 1.

The effect of deficiency or overexpression of antioxidant enzymes on glucose metabolism and insulin sensitivity in mice

Antioxidant	Gene modification	Metabolic phenotype
SOD1	Global KO	Reduction in β-cell volume and insulin secretion/unaltered insulin sensitivity and increased mitochondrial hydrogen peroxide production in muscle [41]
	Global OE	Improved glucose intolerance and reduced skeletal muscle hydrogen peroxide generation and oxidative stress in HFD-fed mice [42]
SOD2	Hz global KO	Impaired insulin secretion, increased ROS in islets, and unaltered insulin sensitivity [43]
	Global OE	Improved glucose intolerance and reduced skeletal muscle oxidative stress in HFD-fed mice [42]
		Unaltered insulin sensitivity and reduced hydrogen peroxide generation in HFD-fed mice [44]
	Skeletal muscle OE	Improved insulin resistance and reduced oxidative stress in the skeletal muscle of rats [45]
Catalase	Global KO	Exacerbated HFD-induced insulin resistance and increased oxidative stress in white adipose tissue [46]
		Accelerated HFD-induced obesity and increased oxidative stress in white adipose tissue [47]
	Global OE	Reduction in fat mass, oxidative stress, and glucose levels in ob/ob mice [48]
	Mitochondrial OE	Improved insulin resistance and reduced hydrogen peroxide generation and oxidative stress in skeletal muscle [44,49]
		Improved insulin resistance and reduced hydrogen peroxide generation and lipid accumulation in the skeletal muscle of HFD-fed mice [50]
SOD2 and	Global SOD2 OE and mitochondrial catalase OE	Improved insulin resistance and reduced hydrogen peroxide generation and oxidative stress in skeletal muscle. No difference in insulin sensitivity or hydrogen peroxide generation compared with that of mitochondrial catalase OE only [44]
catalase
GPx1	Global OE	Increased fat mass and the development of insulin resistance [51]
	Global KO	Improved insulin resistance, enhanced production of ROS and oxidation of PTP [52]
	Liver KO	Improved insulin sensitivity, increased hydrogen peroxide generation in hepatocyte and oxidation of PTP [53]
GPx1 and	Global KO	Prevention of obesity, improved glucose tolerance, and attenuated nonalcoholic fatty liver in HFD-fed mice [54]
catalase
GRx2	Global KO	Exacerbated obesity and insulin resistance in HFD-fed mice/exacerbated oxidative stress by HFD in brain [55]
Prx2	Global KO	Exacerbated aging-induced insulin resistance and oxidative stress in muscle [56]
		Prevented obesity and insulin resistance in HFD-fed mice [57]
		Reduced insulin sensitivity and increased oxidative stress in control diet/no effect on oxidative stress and insulin resistance in HFD-fed mice [58]
Prx3	Global KO	Induced obesity, increased oxidative stress, and impaired glucose tolerance and insulin sensitivity/increased superoxide levels in 3T3-L1 adipocytes [59]
	Global OE	Reduced mitochondrial hydrogen peroxide levels and oxidative stress and improved glucose intolerance [60]
Prx4	Global OE	Improved glucose intolerance in STZ mice and reduced oxidative stress and steatohepatitis in HFD-fed STZ mice [61]
Prx6	Global KO	Reduced insulin secretion and impaired glucose tolerance and insulin sensitivity [62]
MsrA	Global KO	Impaired glucose tolerance and exacerbated insulin resistance and oxidative stress in HFD-fed mice [63]
	Mitochondrial OE	Improved insulin resistance in HFD-fed mice/preserve insulin sensitivity without cytosolic MsrA [64]
	Cytoplasmic OE	Unaltered insulin resistance in HFD-fed mice [64]
MsrB1	Global KO	No effect on insulin sensitivity, hydrogen peroxide levels, or oxidative stress in HFD-fed mice [40]
SelW	Global KO	No change in oxidative stress or insulin sensitivity in the skeletal muscle of HFD-fed mice [39]

SOD1, superoxide dismutase 1; SOD2, superoxide dismutase 2; KO, knockout; OE, overexpression; HFD, high-fat diet; Hz, heterozygous; ROS, reactive oxygen species; GPx, glutathione peroxidase; PTP, protein-tyrosine phosphatase; GRx, glutaredoxin; Prx, peroxiredoxin; STZ mice, streptozotocin-injected mice; Msr, methionine sulfoxide reductase; SelW, selenoprotein W.