Significant Improvement of Insulin Resistance of GK Rats by Treatment with Sodium Selenate

Abstract

We studied the effect of sodium selenate on insulin resistance of Goto-Kakizaki (GK) rats. Rats were kept on standard laboratory chow with and without i.p. injections of sodium selenate (0.173 mg/kg body weight) for 14 days, and then subjected to the glucose clamp. The glucose clamp studies confirmed an improvement in insulin-stimulated glucose disposal in GK rats treated with sodium selenate, with respect to both insulin sensitivity and responsiveness. This amelioration of insulin resistance may be partly due to a direct effect of the sodium selenate on peripheral tissues. 2-Deoxyglucose uptake in sodium selenate-treated adipocytes was increased and the insulin findings suggest that sodium selenate increases not only insulin sensitivity but also insulin responsiveness. Sodium selenate also accelerated glucose incorporation into adipocytes of rats, suggesting that the action of sodium selenate is peripheral. Interestingly, sodium selenate at a high concentration (about 1 mmol/L) was more effective than insulin in enhancing glucose uptake. The present study suggested that sodium selenate treatment led to substantial improvement in peripheral insulin resistance.

Dietary selenate attenuates adiposity and improves insulin sensitivity in high-fat diet-induced obese mice

“…3). Consistent with the previously reported role of selenate in lowering the risk of insulin resistance (Iizuka et al, 2010;Mueller & Pallauf, 2006;Muller et al, 2005;, our results underscore a potential protective effect of selenate against obesity-associated insulin resistance. Although further studies are needed to understand the molecular basis underlying selenate-improved glucose tolerance in HF diet fed mice, improved glucose tolerance shown in the present study appears to be due to selenate-reduced adiposity with altered expression profiles of genes involved in adipokine production and alteration of expression profiles of genes involved in adipokine production and the pro-inflammatory state associated with diet-induced obesity.…”

“…Although previous studies reported a potential insulinlowering effect of selenate in diabetic mice (Iizuka et al, 2010;Mueller & Pallauf, 2006;Muller et al, 2005;, the effect of selenate administration on obesity-associated insulin resistance remained unclear. To address this, we first measured plasma levels of lipid metabolites, glucose and insulin from mice in the three groups.…”

“…In addition, recent studies implicated a potential beneficial role of selenium supplementation in metabolic syndrome such as type 2 diabetes. Selenium, particularly selenate, has been shown to improve insulin sensitivity in diabetic animal models, potentially through its insulinomimetic effect on hepatic energy metabolism (Iizuka, Ueda, Yagi, & Sakurai, 2010;Mueller & Pallauf, 2006;Muller, Most, & Pallauf, 2005;. Intriguingly, recent human studies have shown that high intake of selenium is positively associated with the prevalence of diabetes (Bleys, Navas-Acien, & Guallar, 2007;Stranges et al, 2007), potentially due to its effect on modulation of selenoprotein expression (Zeng et al, 2012) and production of reactive oxygen species .…”

Long-Term Supranutritional Supplementation with Selenate Decreases Hyperglycemia and Promotes Fatty Liver Degeneration by Inducing Hyperinsulinemia in Diabetic db/db Mice

“…However, different forms of selenium have differing effects on insulin-regulated carbohydrate metabolism, indicating various functional mechanisms of selenium compounds. For example, selenate may suppress the increase in fasting plasma glucose concentrations in diabetes models by increasing insulin sensitivity and by acting as an insulin-mimetic in liver and adipose tissue [11], [20],[26], while selenite has been found to stimulate insulin production and secretion from islets and further enhance carbohydrate efficiency via high insulin levels [27]. It has even been reported that selenite may counteract insulin-induced signaling [28].…”

“…Furthermore, selenium has insulin-like properties and could been qualified as a potential antidiabetic agent [9]. Many studies have demonstrated a protective effect of selenium against type 1 and type 2 diabetes [8], and the use of appropriate selenium supplements may improve glucose metabolism by alleviating hyperglycemia, regulating glycolysis and gluconeogenesis, and activating key components of the insulin signaling cascade [10], [11]. On the other hand, more recent findings from large-scale human studies [12]–[14] and animal experiments [15]–[17] have shown that high selenium status or intake is positively correlated with an increased risk of type 2 diabetes.…”