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The biochemical function of Mg 2+ in insulin secretion, insulin signal transduction and insulin resistance Volume 23, numéro 1, March 2010

Auteur
Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Institut für Molekularbiologie und Biochemie, Berlin, Germany

Insulin secretion is started by a Ca 2+ influx that is competitively inhibited by extracellular Mg 2+. This can explain the inverse correlation between serum Mg 2+ and serum insulin concentration. After binding of insulin to its receptor, receptor tyrosine kinase is activated. The autophosphorylation of the receptor kinase and all protein kinases in the insulin signal transduction cascade are dependent on Mg 2+. Besides MgATP as substrate, protein tyrosine kinases are activated by a second Mg 2+. Other protein kinases and some protein phosphatases involved in insulin resistance are dependent on Mg 2+ as well. In the complex action of Mg 2+ on tyrosine protein kinases and serine/threonine kinases, which mediate or inhibit insulin signaling, the concentration of intracellular free Mg 2+ ([Mg 2+] i) may have a permissive function. The secretion of various effectors such as adipokines, interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α), β-adrenergics and reactive oxygen species (ROS) involved in insulin resistance is enhanced in Mg deficiency and obesity. Adipocytes produce chemotactic signals, leading to macrophage recruitment and in addition to adipocytes, to the production of proinflammatory cytokines. The concentration of free fatty acids (FFA), particularly palmitate, is increased in obesity and by the action of β-adrenergics. The complex actions of adipokines, cytokines and palmitate in the induction of insulin resistance are reviewed. The concentration of extracellular and intracellular Mg 2+ in patients and the experimental effects of insulin and catecholamines on [Mg 2+] i in various tissues are described. The controversial effects of different serum Mg 2+ concentrations and Mg 2+ supplementation on plasma glucose and insulin concentration in studies with human subjects and the controversial results of epidemiological studies are reported.