Diabetes Alters the Expression and Translocation of the Insulin-Sensitive Glucose Transporters 4 and 8 in the Atria

Simple item page
dc.contributor.authorZahra Maria
dc.contributor.authorAllison R. Campolo
dc.contributor.authorVeronique A. Lacombe
dc.date.accessioned2017-03-05T22:55:26Z
dc.date.available2017-03-05T22:55:26Z
dc.date.issued2015-12-31
dc.descriptionWe would like to thank Dr. Emilie Martinez and Jill Murray for their excellent technical assistance and animal care.en_US
dc.descriptionen_US
dc.description.abstractAlthough diabetes has been identified as a major risk factor for atrial fibrillation, little is known about glucose metabolism in the healthy and diabetic atria. Glucose transport into the cell, the rate-limiting step of glucose utilization, is regulated by the Glucose Transporters (GLUTs). Although GLUT4 is the major isoform in the heart, GLUT8 has recently emerged as a novel cardiac isoform. We hypothesized that GLUT-4 and -8 translocation to the atrial cell surface will be regulated by insulin and impaired during insulin-dependent diabetes. GLUT protein content was measured by Western blotting in healthy cardiac myocytes and type 1 (streptozotocin-induced, T1Dx) diabetic rodents. Active cell surface GLUT content was measured using a biotinylated photolabeled assay in the perfused heart. In the healthy atria, insulin stimulation increased both GLUT-4 and -8 translocation to the cell surface (by 100% and 240%, respectively, P<0.05). Upon insulin stimulation, we reported an increase in Akt (Th308 and s473 sites) and AS160 phosphorylation, which was positively (P<0.05) correlated with GLUT4 protein content in the healthy atria. During diabetes, active cell surface GLUT-4 and -8 content was downregulated in the atria (by 70% and 90%, respectively, P<0.05). Akt and AS160 phosphorylation was not impaired in the diabetic atria, suggesting the presence of an intact insulin signaling pathway. This was confirmed by the rescued translocation of GLUT-4 and -8 to the atrial cell surface upon insulin stimulation in the atria of type 1 diabetic subjects. In conclusion, our data suggest that: 1) both GLUT-4 and -8 are insulin-sensitive in the healthy atria through an Akt/AS160 dependent pathway; 2) GLUT-4 and -8 trafficking is impaired in the diabetic atria and rescued by insulin treatment. Alterations in atrial glucose transport may induce perturbations in energy production, which may provide a metabolic substrate for atrial fibrillation during diabetes.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationMaria Z, Campolo AR, Lacombe VA (2015) Diabetes Alters the Expression and Translocation of the Insulin-Sensitive Glucose Transporters 4 and 8 in the Atria. PLoS ONE 10(12): e0146033. doi:10.1371/journal.pone.0146033en_US
dc.identifier.doi10.1371/journal.pone.0146033en_US
dc.identifier.urihttp://hdl.handle.net/11244/49285
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(12): e0146033
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0146033
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectDiabetes mellitus,Insulin,Membrane proteins,Glucose,Insulin signaling,Protein expression,Type 1 diabetes,Muscle cellsen_US
dc.titleDiabetes Alters the Expression and Translocation of the Insulin-Sensitive Glucose Transporters 4 and 8 in the Atriaen_US
dc.typeResearch Articleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
journal.pone.0146033.pdf
Size:
2.35 MB
Format:
Adobe Portable Document Format
Download

Collections

OU - Faculty and Staff Publications