Tungstate Reduces the Expression of Gluconeogenic Enzymes in STZ Rats

Nocito, Laura; Zafra, Delia; Calbó, Joaquim; Domínguez, Jorge; Guinovart, Joan J.

doi:10.1371/journal.pone.0042305

Cited by 23 publications

(38 citation statements)

References 42 publications

(57 reference statements)

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“…Prior studies have pointed to different target tissues for tungstate actions depending on the model investigated. Thus, tungstate has been shown to normalize hepatic glucose metabolism in streptozotocin (STZ) and Zucker diabetic rats (5,20,37) to improve ␤-cell function in neonatal and adult STZtreated rats (1,3,21) or to modulate energy homeostasis in obese rats (2,7,18). Remarkably, the normoglycemic effects of tungstate in STZ-treated rats were associated with an increase in ␤-cell mass (3,21).…”

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confidence: 99%

Tungstate promotes β-cell survival inIrs2^−/−mice

Oliveira

Rebuffat

Gasa

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Pancreatic β-cells play a central role in type 2 diabetes (T2D) development, which is characterized by the progressive decline of the functional β-cell mass that is associated mainly with increased β-cell apoptosis. Thus, understanding how to enhance survival of β-cells is key for the management of T2D. The insulin receptor substrate-2 (IRS-2) protein is pivotal in mediating the insulin/IGF signaling pathway in β-cells. In fact, IRS-2 is critically required for β-cell compensation in conditions of increased insulin demand and for β-cell survival. Tungstate is a powerful antidiabetic agent that has been shown to promote β-cell recovery in toxin-induced diabetic rodent models. In this study, we investigated whether tungstate could prevent the onset of diabetes in a scenario of dysregulated insulin/IGF signaling and massive β-cell death. To this end, we treated mice deficient in IRS2 ( Irs2−/−), which exhibit severe β-cell loss, with tungstate for 3 wk. Tungstate normalized glucose tolerance in Irs2−/− mice in correlation with increased β-cell mass, increased β-cell replication, and a striking threefold reduction in β-cell apoptosis. Islets from treated Irs2−/− exhibited increased phosphorylated Erk1/2. Interestingly, tungstate repressed apoptosis-related genes in Irs2−/− islets in vitro, and ERK1/2 blockade abolished some of these effects. Gene expression profiling showed evidence of a broad impact of tungstate on cell death pathways in islets from Irs2−/− mice, consistent with reduced apoptotic rates. Our results support the finding that β-cell death can be arrested in the absence of IRS2 and that therapies aimed at reversing β-cell mass decline are potential strategies to prevent the progression to T2D.

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confidence: 99%

Tungstate promotes β-cell survival inIrs2^−/−mice

Oliveira

Rebuffat

Gasa

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Hepatic gluconeogenesis has an important influence on glucose metabolism [37]. Additionally, insulin deficiency is closely correlated with hepatic glucose output via increased expression of PEPCK that is a key enzyme of hepatic carbohydrate metabolism in diabetic hyperglycemia [28, 38, 39]. Liver-specific inhibition of PEPCK with RNAi improved diabetic hyperglycemia [40].…”

Section: Discussionmentioning

confidence: 99%

Decrease of Plasma Glucose byHibiscus taiwanensisin Type-1-Like Diabetic Rats

Wang

Chung

Cheng

2013

Evidence-Based Complementary and Alternative Medicine

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Hibiscus taiwanensis (Malvaceae) is widely used as an alternative herb to treat disorders in Taiwan. In the present study, it is used to screen the effect on diabetic hyperglycemia in streptozotocin-induced diabetic rats (STZ-diabetic rats). The extract of Hibiscus taiwanensis showed a significant plasma glucose-lowering action in STZ-diabetic rats. Stems of Hibiscus taiwanensis are more effective than other parts to decrease the plasma glucose in a dose-dependent manner. Oral administration of Hibiscus taiwanensis three times daily for 3 days into STZ-diabetic rats increased the sensitivity to exogenous insulin showing an increase in insulin sensitivity. Moreover, similar repeated administration of Hibiscus taiwanensis for 3 days in STZ-diabetic rats produced a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Taken together, our results suggest that Hibiscus taiwanensis has the ability to lower plasma glucose through an increase in glucose utilization via elevation of skeletal GLUT 4 and decrease of hepatic PEPCK in STZ-diabetic rats.

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“…The concentration of Na 2 WO 4 used to evaluate the antidiabetic effect was around 6 mM [18,19]. Toxicity was not reported in animal studies [17,18,45] or in vitro [20] as an antidiabetic agent. Moreover, Na 2 WO 4 was studied in obese nondiabetic patients without any toxicity effect [46].…”

Section: Figmentioning

confidence: 99%

“…Therefore, insulin mimetics have been sought. Sodium tungstate (Na 2 WO 4 ) is a water soluble inorganic compound that can exert an insulin-like effect in diabetes [16,17]. Several studies have shown that oral administration of Na 2 WO 4 into animal models of type 1 and type 2 diabetes normalizes glycemia without hypoglycemia [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

Khader

Sherman

Rameshwar

et al. 2016

Stem Cells and Development

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Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na 2 WO 4 ), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin. Na 2 WO 4 was added to the media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic differentiation was assessed by biochemical analyses, immunostaining, and gene expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS) was also investigated. The chondrogenic differentiation of MSCs was enhanced in the presence of low concentrations of Na 2 WO 4 compared to control, without Na 2 WO 4 . In the induction medium containing insulin, cells in 0.01 mM Na 2 WO 4 produced significantly higher sulfated glycosaminoglycans, collagen type II, and chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM Na 2 WO 4 had significantly higher collagen II production and significantly higher sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and induction medium without insulin containing low concentrations of Na 2 WO 4 also expressed chondrogenic markers. Na 2 WO 4 did not stimulate PBMC proliferation or apoptosis. The results demonstrate that Na 2 WO 4 enhances chondrogenic differentiation of MSCs, does not have a toxic effect, and may be useful for MSC-based approaches for cartilage repair.

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Tungstate Reduces the Expression of Gluconeogenic Enzymes in STZ Rats

Cited by 23 publications

References 42 publications

Tungstate promotes β-cell survival inIrs2^−/−mice

Tungstate promotes β-cell survival inIrs2^−/−mice

Decrease of Plasma Glucose byHibiscus taiwanensisin Type-1-Like Diabetic Rats

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

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Tungstate Reduces the Expression of Gluconeogenic Enzymes in STZ Rats

Cited by 23 publications

References 42 publications

Tungstate promotes β-cell survival inIrs2−/−mice

Tungstate promotes β-cell survival inIrs2−/−mice

Decrease of Plasma Glucose byHibiscus taiwanensisin Type-1-Like Diabetic Rats

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

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Tungstate promotes β-cell survival inIrs2^−/−mice

Tungstate promotes β-cell survival inIrs2^−/−mice