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  • Title: Signaling pathway involved in the activation of heart 6-phosphofructo-2-kinase by insulin.
    Author: Lefebvre V, Méchin MC, Louckx MP, Rider MH, Hue L.
    Journal: J Biol Chem; 1996 Sep 13; 271(37):22289-92. PubMed ID: 8798384.
    Abstract:
    Incubation of isolated rat cardiomyocytes with insulin increased 2-deoxyglucose uptake, glycogen synthesis, and fructose 2, 6-bisphosphate content. Half-maximal effects were obtained with 1-2 nM insulin. The insulin-induced increase in fructose 2,6-bisphosphate content was preceded by a 2-3-fold activation of 6-phosphofructo-2-kinase, which was independent of glucose transport. Insulin activated phosphatidylinositol 3-kinase and p70 ribosomal S6 kinase (p70 S6 kinase), but had no significant effect on mitogen-activated protein kinase, although phorbol 12-myristate 13-acetate activated the latter. The effect of insulin on fructose 2, 6-bisphosphate, 6-phosphofructo-2-kinase, and phosphatidylinositol 3-kinase was blocked by wortmannin. However, rapamycin, which inhibited p70 S6 kinase activation, and PD 98059, an inhibitor of the mitogen-activated protein kinase pathway, had no effect on the insulin-induced activation of 6-phosphofructo-2-kinase. Heart 6-phosphofructo-2-kinase can therefore be regarded as a glycolytic target of insulin. Its activation by insulin might be mediated by phosphatidylinositol 3-kinase.
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