Tyrosine phosphatase inhibitors, vanadate and pervanadate, stimulate glucose transport and GLUT translocation in muscle cells by a mechanism independent of phosphatidylinositol 3-kinase and protein kinase C.

Tsiani, Evangelia; Bogdanovic, Elena; Sorisky, Alexander; Nagy, Laura; Fantus, I. George

doi:10.2337/diabetes.47.11.1676

Cited by 105 publications

(93 citation statements)

References 63 publications

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“…Recent data suggest that this enzyme modulates the intrinsic activity of GLUT4 and, thus, the stimulation of glucose uptake by insulin in skeletal muscle (36) and 3T3-L1 adipocytes (34,40). In contrast, vanadate-mediated glucose uptake has been shown to be independent of p38 MAPK activation (43). Together, these results suggest that acute vanadate stimulation of glucose uptake occurs through the activation of a different signaling pathway than insulin.…”

mentioning

confidence: 47%

“…Acute activation of glucose transport by millimolar concentrations of vanadate has been observed in many tissues, including adipocytes, cardiomyocytes, and skeletal muscle (19,20,31,41,43). However, chronic vanadate exposure could stimulate glucose uptake at different concentrations from the one observed for acute exposure.…”

Section: Resultsmentioning

confidence: 99%

“…One of the effectors of PI 3-kinase signaling is the protein kinase B (PKB)/Akt (2). It has been demonstrated that recruitment of glucose transporter vesicles by insulin (8,14,17,44) but not vanadate (43) requires PKB/Akt activation. In addition to the IRS-1/PI 3-kinase pathway, insulin also activates p38 MAPK.…”

mentioning

confidence: 99%

“…In contrast, the role of PI 3-kinase in the regulation of glucose uptake by vanadate is still controversial. Studies with wortmannin have demonstrated that, although vanadate mediates PI 3-kinase activation, this step is not required for the stimulation of glucose uptake (9,43). One of the effectors of PI 3-kinase signaling is the protein kinase B (PKB)/Akt (2).…”

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confidence: 99%

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Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Tardif

Julien

Chiasson

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Coderre. Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation. Am J Physiol Endocrinol Metab 284: E1055-E1064, 2003. First published December 10, 2002 10.1152 10. /ajpendo.00134.2002 inhibitor of tyrosine phosphatases, has insulin-mimetic properties. It has been shown that acute vanadate administration enhances glucose uptake independently of phosphatidylinositol (PI) 3-kinase and p38 MAPK. However, therapeutic vanadate use requires chronic administration, and this could potentially involve a different signaling pathway(s). Thus, we examined the mechanisms by which chronic vanadate exposure (16 h) stimulates glucose uptake in primary cultures of adult cardiomyocytes. The effect of vanadate on the activation of insulin-signaling molecules was evaluated 60 min after its withdrawal and in the absence of insulin. We therefore evaluated the persistent effect of vanadate on the insulin-signaling cascade. Our results demonstrate that preincubation with low vanadate concentrations (25-75 M) induces a dose-dependent increase in glucose uptake. The augmentation of this process was not due to alterations in GLUT1 or GLUT4 protein levels, transcription, or de novo protein synthesis. Chronic vanadate exposure was associated with activation of the insulin receptor, insulin receptor substrate-1 (IRS-1), PKB/Akt, and p38 MAPK. Furthermore, inhibition of PI 3-kinase or p38 MAPK by wortmannin and PD-169316, respectively, significantly inhibited vanadate-mediated glucose uptake in cardiomyocytes. Thus, over time, different (albeit overlapping) signaling cascades may be activated by vanadate. insulin signaling; protein kinase B/Akt; diabetes; vanadium; heart; phosphatidylinositol 3-kinase DESPITE THE ABILITY OF THE HEART to use multiple substrates to meet its energy requirements, this organ has one of the highest rates of glucose utilization in vivo (18,45). Decreased glucose uptake has been observed in both type 1 and type 2 diabetic subjects (25,29,45), and it has been proposed that abnormal regulation of this process has a role in the development of cardiac dysfunction (13). In db/db mice, a model of type 2 diabetes characterized by a reduction in glucose utilization and myocardial dysfunction, selective overexpression of the major glucose transporter GLUT4 expressed in the heart normalized these abnormalities (4). Interestingly, vanadate administration to streptozotocin-induced diabetic rats improved both insulin action and myocardial function in these animals (49). Furthermore, it has been shown that chronic vanadate exposure augments glucose uptake and improves ischemic tolerance in the hypertrophied heart (41). Together, these data suggest that glucose is an important cardiac substrate and that vanadate, by stimulating glucose uptake, could have a beneficial effect on the diabetic heart.Vanadium is a trace element found in most cells in concentrations ranging from 0.1 to 1 M (31). Vanadium compounds, such as vanadate, are inhibitors of protein tyrosine...

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mentioning

confidence: 47%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Tardif

Julien

Chiasson

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…Surprisingly, there is little evidence of any effect of agents being capable of stimulating glucose transport on the activation of Akt1. A recent report showed that vanadium compounds activated Akt1 and this activation was inhibited by wortmannin [54]. This is, however, inconsequential for glucose transport because the stimulation of glucose transport by vanadate is wortmannin-insensitive [55].…”

Section: Discussionmentioning

confidence: 99%

Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by α-lipoic acid in 3T3-L1 adipocytes

et al. 2000

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Insulin spelling regulates glucose uptake into fat and muscle cells through the recruitment of glucose transporter (GLUT)4 from an intracellular membrane storage pool to the plasma membrane [1±3]. The first critical step in the stimulation of glucose transport is activation of the insulin receptor intrinsic tyrosine kinase. The activated receptor phosphorylates endogenous substrate proteins, primarily members of the insulin receptor substrate (IRS) family [4]. Tyrosine phosphorylation within multiple YXXM and YMXM motifs on the IRS proteins provide docking AbstractAims/hypothesis. A natural cofactor of mitochondrial dehydrogenase complexes and a potent antioxidant, a-lipoic acid improves glucose metabolism in people with Type II (non-insulin-dependent) diabetes mellitus and in animal models of diabetes. In this study we investigated the cellular mechanism of action of a-lipoic acid in 3T3-L1 adipocytes. Methods. We treated 3T3-L1 adipocytes with 2.5 mmol/l R (+) a-lipoic acid for 2 to 60 min, followed by assays of: 2-deoxyglucose uptake; glucose transporter 1 and 4 (GLUT1 and GLUT4) subcellular localization; tyrosine phosphorylation of the insulin receptor or of the insulin receptor substrate-1 in cell lysates; association of phosphatidylinositol 3-kinase activity with immunoprecipitates of proteins containing phosphotyrosine or of insulin receptor substrate-1 using a in vitro kinase assay; association of the p85 subunit of phosphatidylinositol 3-kinase with phosphotyrosine proteins or with insulin receptor substrate-1; and in vitro activity of immunoprecipitated Akt1. The effect of R (+) a-lipoic acid was also compared with that of S(±) a-lipoic acid.Results. Short-term treatment of 3T3-L1 adipocytes with R (+) a-lipoic acid rapidly stimulated glucose uptake in a wortmannin-sensitive manner, induced a redistribution of GLUT1 and GLUT4 to the plasma membrane, caused tyrosine phosphorylation of insulin receptor substrate-1 and of the insulin receptor, increased the antiphosphotyrosine-associated and insulin receptor substrate-1 associated phosphatidylinositol 3-kinase activity and stimulated Akt activity. Conclusion/interpretation. These results indicate that R (+) a-lipoic acid directly activates lipid, tyrosine and serine/threonine kinases in target cells, which could lead to the stimulation of glucose uptake induced by this natural cofactor. These properties are unique among all agents currently used to lower glycaemia in animals and humans with diabetes. [Diabetologia (2000) 43: 294±303]

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Role of the actin cytoskeleton in insulin action

Tsakiridis¹,

Tong²,

Matthews³

et al. 1999

Microsc. Res. Tech.

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Insulin has diverse effects on cells, including stimulation of glucose transport, gene expression, and alterations of cell morphology. The hormone mediates these effects by activation of signaling pathways which utilize, 1) adaptor molecules such as the insulin receptor substrates (IRS), the Src and collagen homologs (Shc), and the growth factor receptor binding protein 2 (Grb2); 2) lipid kinases such as phosphatidylinositol 3‐kinase (PI 3‐Kinase); 3) small G proteins; and 4) serine, threonine, and tyrosine kinases. The activation of such signaling molecules by insulin is now well established, but we do not yet fully understand the mechanisms integrating these seemingly diverse pathways. Here, we discuss the involvement of the actin cytoskeleton in the propagation and regulation of insulin signals. In muscle cells in culture, insulin induces a rapid actin filament reorganization that coincides with plasma membrane ruffling and intense accumulation of pinocytotic vesicles. Initiation of these effects of insulin requires an intact actin cytoskeleton and activation of PI 3‐kinase. We observed recruitment PI 3‐kinase subunits and glucose transporter proteins to regions of reorganized actin. In both muscle and adipose cells, actin disassembly inhibited early insulin‐induced events such as recruitment of glucose transporters to the cell surface and enhanced glucose transport. Additionally, actin disassembly inhibited more prolonged effects of insulin, including DNA synthesis and expression of immediate early genes such as c‐fos. Intact actin filaments appear to be essential for mediation of early events such as association of Shc with Grb2 in response to insulin, which leads to stimulation of gene expression. Preliminary observations support a role for focal adhesion signaling complexes in insulin action. These observations suggest that the actin cytoskeleton facilitates propagation of the morphological, metabolic, and nuclear effects of insulin by regulating proper subcellular distribution of signaling molecules that participate in the insulin signaling pathway. Microsc. Res. Tech. 47:79–92, 1999. © 1999 Wiley‐Liss, Inc.

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Tyrosine phosphatase inhibitors, vanadate and pervanadate, stimulate glucose transport and GLUT translocation in muscle cells by a mechanism independent of phosphatidylinositol 3-kinase and protein kinase C.

Cited by 105 publications

References 63 publications

Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation

Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by α-lipoic acid in 3T3-L1 adipocytes

Role of the actin cytoskeleton in insulin action

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