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Insulin signal mimicry as a mechanism for the insulin-like effects of vanadium

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Abstract

Among several metals, vanadium has emerged as an extremely potent agent with insulin-like properties. These insulin-like properties have been demonstrated in isolated cells, tissues different animal models of type I and type II diabetes as well as a limited number of human subjects. Vanadium treatment has been found to improve abnormalities of carbohydrate and lipid metabolism and of gene expression in rodent models of diabetes. In isolated cells, it enhances glucose transport, glycogen and lipid synthesis, and inhibits gluconeogenesis and lipolysis. The molecular mechanism responsible for the insulin-like effects of vanadium compounds have been shown to involve the activation of several key components of insulin-signaling pathways that include the mitogen-activated-protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK, and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB). It is interesting that the vanadium effect on these signaling systems is independent of insulin receptor protein tyrosine kinase activity, but it is associated with enhanced tyrosine phosphorylation of insulin receptor substrate-1. These actions seem to be secondary to vanadium-induced inhibition of protein tyrosine phosphatases. Because MAPK and PI3-K/PKB pathways are implicated in mediating the mitogenic and metabolic effects of insulin, respectively, it is plausible that mimicry of these pathways by vanadium serves as a mechanism for its insulin-like responses.

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Author notes

  1. Sanjay K. Pandey

    Present address: Metabolic Disease Program, Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA

  2. Jean-François Théberge

    Present address: McGill Cancer Centre, McGill University, Montreal, Quebec, Canada

Authors and Affiliations

  1. Laboratory of Cell Signaling, Research Centre, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Montreal, Quebec, Canada

    Mohamad Z. Mehdi, Sanjay K. Pandey, Jean-François Théberge & Ashok K. Srivastava

  2. Department of Medicine, Université de Montréal, Montreal, Quebec, Canada

    Mohamad Z. Mehdi, Sanjay K. Pandey, Jean-François Théberge & Ashok K. Srivastava

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Mehdi, M.Z., Pandey, S.K., Théberge, JF. et al. Insulin signal mimicry as a mechanism for the insulin-like effects of vanadium. Cell Biochem Biophys 44, 73–81 (2006). https://doi.org/10.1385/CBB:44:1:073

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