GLUT4 , AMP kinase , but not the insulin receptor , are required for hepatoportal glucose sensor – stimulated muscle glucose utilization

  • Burcelin R
  • Crivelli V
  • Perrin C
 et al. 
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Recent evidence suggests the existence of a hepatoportal vein glucose sensor, whose activation leads to enhanced glucose use in skeletal muscle, heart, and brown adipose tissue. The mecha- nism leading to this increase in whole body glucose clearance is not known, but previous data sug- gest that it is insulin independent. Here, we sought to further determine the portal sensor sig- naling pathway by selectively evaluating its dependence on muscle GLUT4, insulin receptor, and the evolutionarily conserved sensor of metabolic stress, AMP-activated protein kinase (AMPK). We demonstrate that the increase in muscle glucose use was suppressed in mice lacking the expression of GLUT4 in the organ muscle. In contrast, glucose use was stimulated normally in mice with muscle-specific inactivation of the insulin receptor gene, confirming independence from insulin-signaling pathways. Most importantly, the muscle glucose use in response to acti- vation of the hepatoportal vein glucose sensor was completely dependent on the activity of AMPK, because enhanced hexose disposal was prevented by expression of a dominant negative AMPK in muscle. These data demonstrate that the portal sensor induces glucose use and development of hypoglycemia independently of insulin action, but by a mechanism that requires activation of the AMPK and the presence of GLUT4

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  • Rémy Burcelin

  • Valerie Crivelli

  • Christophe Perrin

  • Anabela Da Costa

  • James Mu

  • Barbara B Kahn

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