Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 15, Issue 1-4, Pages 51-58Publisher
KARGER
DOI: 10.1159/000083638
Keywords
insulin; GLUT2; receptor-transporter complex; hepatic glucose production; hepatocytes
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Funding
- NIDDK NIH HHS [DK56212, DK50230, DK30995] Funding Source: Medline
- NINDS NIH HHS [NS39918] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK050230, R01DK056212] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS039918] Funding Source: NIH RePORTER
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The hepatic glucose transporter, GLUT2, facilitates bidirectional glucose transport across the hepatocyte plasma membrane under insulin regulation. We studied the interactions of IR and GLUT2 proteins to determine whether they are physically coupled in a receptor- transporter complex. By comparing endosome and plasma membrane IR and GLUT2 ratios before and after feeding, it was determined that IR and GLUT2 are internalized in a fixed ratio. When solubilized hepatocytes were immunoprecipitated with antibodies against either IR or GLUT2, both proteins co- precipitated. The association of IR and GLUT2 was further assessed by confocal microscopy. Sections of fed liver were incubated with fluorescein- tagged anti- GLUT2 or Texas Red- tagged anti- IR. Colocalization was observed both at the plasma membrane and in the cytosol. Fluorescence-resonance energy transfer studies further confirmed this association. We conclude that IR and GLUT2 form a receptor- transporter complex in hepatocytes, which forms a mechanism of insulin- mediated hepatic glucose regulation. Copyright (C) 2005 S. Karger AG, Basel.
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