Effect of Sodium Selenite Supplementation on Glucose Intolerance and Pancreatic Oxidative Stress in Type 2 Diabetic Mice under Different Selenium Status

et al. 2018

Self Cite

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...

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Murano

Ogino

et al. 2018

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“…However, in this study, SeMet may not restore GPX1 expressions in these organs to the normal levels because it is hard to recover Se status in the deficient diet-fed mice to that in the normal diet-fed mice by Se ingestion. 35) A reversible oxidation and reduction of protein tyrosine phosphatases by ROS production and expressions of oxidative stress-elimination enzymes in insulin target tissues affect the insulin signaling. 36) This may contribute to the hypoglycemic effect of supplementary SeMet under insufficient Se status.…”

Section: Discussionmentioning

confidence: 99%

Effect of Seleno-L-methionine on Oxidative Stress in the Pancreatic Islets of a Short-Term Induced Diabetic Mouse Model in Insufficient Selenium Status

Ueno

Shimizu

et al. 2018

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The protective effects of seleno-L-methionine (SeMet) on oxidative stress in pancreatic islets were investigated with a short-term nicotinamide (NA) and streptozotocin (STZ)-induced diabetic mouse model. ICR mice were intraperitoneally injected twice with 100 mg/kg STZ and 120 mg/kg NA at a 1-d interval and were then orally administered 158 µg Se/kg SeMet with free access to a selenium-deficient diet for 5 weeks. Administration of SeMet significantly improved the levels of glycated hemoglobin (HbA1c), non-fasting and oral glucose tolerance-tested (OGTT) blood glucose, plasma adiponectin and hepatic glycogen that deteriorated by NA/STZ treatment. However, supplementary SeMet did not restore non-fasting plasma insulin levels in NA/STZ treatment group and significantly suppressed OGTT plasma insulin levels in the control group. Although SeMet significantly suppressed 8-hydroxy-2′-deoxyguanosine density in pancreatic islets, SeMet did not restore insulin density. The hepatic and pancreatic mRNA levels of glutathione peroxidase 1 (GPX1) increased by NA/STZ treatment or SeMet administration. These results suggest that although a physiological level of SeMet improves glucose tolerance by exhibiting insulin-mimetic activity in a short-term induced diabetic mouse model under insufficient Se status, the suppression of pancreatic oxidative stress with the induction GPX1 by SeMet supplementation is unlikely to restore insulin storage and secretion.Key words selenium; diabetes; insulin; glutathione peroxidase 1; seleno-L-methionine; oxidative stress Selenium (Se) is one of the essential micronutrients for human and animals and exerts as a key component of selenoproteins to regulate many physiological functions.1) The families of glutathione (GSH) peroxidase (GPX) and thioredoxin reductase (TR) are the well-known Se-dependent antioxidant enzymes.2,3) GPX1 is particularly important because the antioxidant enzyme has the higher affinity than catalase for hydrogen peroxide (H 2 O 2 ) 4) that is formed by superoxide dismutase from superoxide anions 5) or directly generated by oxidative stress in cytoplasm. Therefore, Se deficiency induces some pathological conditions including cancer and cardiovascular disease.6) The patients with Se-deficiency syndrome, Keshan disease cause cardiomyopathy with the pancreatic atrophy and degeneration.7) The fragility for the oxidative stress in pancreas may be responsible for the pathogenesis. 8)The early stages of type 2 diabetes is characterized by postprandial hyperglycemia by insufficient secretion of insulin from pancreatic β-cells and by the poor response on the target organs.9,10) As the etiology of type 2 diabetes is linked to genetic and lifestyle factors, 11,12) the onset is preventable through the improvements of dietary habits and lifestyle.13) However, deteriorations in dietary habits and lifestyle are involved with oxidative stress 14) and thereby connected with the onset of diabetes.15) Increased generation of reactive oxygen species (ROS) promotes a functional disorder in pancreat...

“…Only SeMet-supplemented mice exceeded the normal diet-feeding mice in the Se content and GPX1 activity of NA/ STZ-untreated groups, as compared with NSY mice that were established as an inbred strain with spontaneous development of diabetes from ICR mice. 27) As cystathionine γ-lyase activity is known to be relatively high in the liver and pancreas, 39) methylselenol may easily be formed from SeMet in these tissues. In our previous study, the activity of GPX4 and TR in the pancreas was negligible.…”

Section: )mentioning

confidence: 99%

Effects of Administering Sodium Selenite, Methylseleninic Acid, and Seleno-L-methionine on Glucose Tolerance in a Streptozotocin/Nicotinamide-Induced Diabetic Mouse Model

Ueno

Shimizu

et al. 2014

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The effects of administering the selenocompounds, sodium selenite, methylseleninic acid (MSA), and seleno-L-methionine (SeMet) on glucose tolerance were compared in the nicotinamide (NA) and streptozotocin (STZ)-induced diabetic mouse model. ICR mice were intraperitoneally treated twice with STZ (100 mg/ kg) 15 min after an injection of NA (120 mg/kg) at a 1-d interval. Non-fasting blood glucose levels were then monitored weekly while orally administering the selenocompounds at 158 µg Se/kg body weight with free access to a selenium-deficient diet for 5 weeks. The mean body weights of NA/STZ-induced diabetic mice were partly restored by the administration of selenocompounds, while SeMet led to a higher selenium content and glutathione peroxidase 1 activity in the pancreas. Non-fasting and oral glucose tolerance-tested blood glucose levels, which were elevated by NA/STZ, were significantly suppressed by the administration of SeMet. These results suggest that SeMet may improve glucose tolerance in a NA/STZ-induced mild diabetic mouse model by increasing bioavailability in the pancreas.