Role of Supplementary Selenium on the Induction of Insulin Resistance and Oxidative Stress in NSY Mice Fed a High Fat Diet

Abstract

The role of supplementary selenium on the induction of insulin resistance and oxidative stress in a diabetic mouse model was investigated in NSY mice on a high fat diet (HFD) and administered seleno-L-methionine (SeMet)-containing water for 12 weeks. Significant increases in oral glucose tolerance-tested (OGTT), insulin tolerance-tested, and non-fasting blood glucose levels were observed in mice on a HFD, as well as the significant increases in OGTT and non-fasting plasma insulin levels. Mice on a HFD had decreased plasma adiponectin levels and increased free fatty acid (FFA) levels. Supplementary SeMet significantly augmented OGTT blood glucose levels in mice on a HFD and plasma FFA levels in mice on a normal diet. The mRNA levels of six selenoproteins were measured, and glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were selected as candidates that may be associated with insulin resistance or oxidative stress in the liver. Hepatic GPx1 expression was elevated in mice on a HFD and SeMet supplementation, and SelP expression increased in mice on a HFD. Histopathological observations in hepatic tissues showed hypertrophy of parenchymal cells and significant expression of 4-hydroxy-2-nonenal in mice on a HFD, indicating lipid accumulation and oxidative stress induction. Hepatic protein tyrosine phosphatase activity also increased by a HFD. These results suggest that hepatic lipid accumulation in NSY mice on a HFD promoted oxidative stress and hepatic SelP expression, and supplementary SeMet induced hepatic GPx1 expression.Key words selenium; diabetes; insulin resistance; glutathione peroxidase 1; selenoprotein P; oxidative stress Type 2 diabetes mellitus is a metabolic disease associated with genetic and lifestyle factors 1) caused by the decline in insulin potency in organs, such as liver, muscle, and adipose tissue, and/or reduced insulin secretion from pancreatic β-cells. 2)This disease leads to diabetic peripheral neuropathy, nephropathy, and retinopathy by raising the level of blood glucose, and eventually gangrene, renal failure, and blindness.3) These pathologies are linked on an individual level to obesity and overweight, 4) on a physiological level to insulin resistance, 5) and on a cellular level to oxidative stress. 6) Insulin-resistant diabetes is a state of declined glucose uptake in target tissue cells, which do not properly respond to insulin and do not have a functioning insulin transduction system. 7) Intracellular production of reactive oxygen species (ROS) and redox activation of protein tyrosine phosphatase (PTP) 1B are involved in the decline of insulin signal transduction phosphorylation [8][9][10] and dysfunction in pancreatic β-cells. 11,12) Selenium (Se) is an essential trace element and functions as a key component of critical enzymes for redox homeostasis and protection from oxidative stress, which include the glutathione peroxidase (GPx) family and selenoprotein P (SelP). 13,14) GPx1 is located in the cytosol to remove hydrogen peroxide (H 2 O 2 ), which is generated by intrac...

Selenium Status Is Associated With Insulin Resistance Markers in Adults: Findings From the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES)

“…In our analysis, only markers of insulin resistance (insulin concentration and HOMA-IR), but not glucose, were associated with selenium in the fully adjusted model. Our findings corroborate the hypothesis that high selenium status disturbs insulin metabolism leading to hyperinsulinemia ( 27 , 28 ), but the effect on glucose is not as strong, as it can be mitigated when controlling strong risk factors for T2DM such as body weight and metabolic syndrome. In our study, no association between selenium status and the prevalence of diabetes was observed, which counteracts the findings reported in two other studies conducted in the NHANES population ( 18 , 29 ).…”

“…These studies have associated the upregulation of the selenoproteins glutathione peroxidase 1 (GPX1), methionine sulfoxide reductase B1 (MSRB1), selenoprotein S (SELENOS) ( 27 ) and selenoprotein P (SELENOP) ( 30 ) induced by high selenium intake with hyperglycaemia, decreased insulin sensitivity and liver triglyceride concentrations. It was hypothesized that increased synthesis of these antioxidant selenoproteins diminishes intracellular reactive oxygen species derived from glucose metabolism and disturbs key regulators of pancreatic beta-cells, leading to chronic hyperinsulinaemia ( 27 , 28 ). An experimental animal model of diabetes revealed that neutralization of SELENOP improved glucose tolerance and insulin secretion ( 31 ), suggesting that this selenoprotein may play a particularly important role in the pathogenesis of T2DM.…”

Life Under Hypoxia Lowers Blood Glucose Independently of Effects on Appetite and Body Weight in Mice

“…Plasma adiponectin showed a minor increase in association with HFD induced obesity (chow ad libitum vs. HFD ad libitum ; Figure 3C), which is at variance to most, but not all reports from the literature [e.g. (33–36)], and which was reversed with amelioration of obesity by hypoxia or restricted feeding (Figure 3C). Obesity distinctly increased plasma FGF-21 (chow ad libitum vs. HFD ad libitum ; Figure 3D), which showed a trend toward higher concentrations under exposure to hypoxia than under food restriction (pmol/l: hypoxia, 44.1 ± 9.5, vs. weight matched control, 23.7 ± 3.6; p = 0.058; Figure 3D).…”

The Antioxidant Effect of PLGA Nanoparticles Encapsulated with Lutein in Rats Treated with Hypercaloric Diet

“…MDA levels were 0.018±0.005 nmol/g protein for O group; 0.016±0.005 nmol/g protein for N group; 0.01±0.005 nmol/g protein for L group for spleen and 0.031±0.004 nmol/g protein for O group; 0.02±0.004 nmol/g protein for N group; 0.017±0.004 nmol/g protein for L group for liver. This study was based on the premise that a hypercaloric diet induce oxidative stress in rats causing hepatic steatosis and cellular hypertrophy as shown in previous studies [34,35]. Our working hypothesis was that PLGA NP's loaded with lutein increase the antioxidant defenses due to lutein antioxidant potential [25].…”