title: GLUT12 functions as a basal and insulin-independent glucose transporter in the heart.
abstract: Glucose uptake from the bloodstream is the rate-limiting step in whole body glucose utilization, and is regulated by a family of membrane proteins called glucose transporters (GLUTs). Although GLUT4 is the predominant isoform in insulin-sensitive tissues, there is recent evidence that GLUT12 could be a novel second insulin-sensitive GLUT. However, its physiological role in the heart is not elucidated and the regulation of insulin-stimulated myocardial GLUT12 translocation is unknown. In addition, the role of GLUT12 has not been investigated in the diabetic myocardium. Thus, we hypothesized that, as for GLUT4, insulin regulates GLUT12 translocation to the myocardial cell surface, which is impaired during diabetes. Active cell surface GLUT (-4 and -12) content was quantified (before and after insulin stimulation) by a biotinylated photolabeled assay in both intact perfused myocardium and isolated cardiac myocytes of healthy and type 1 diabetic rodents. GLUT localization was confirmed by immunofluorescent confocal microscopy, and total GLUT protein expression was measured by Western blotting. Insulin stimulation increased translocation of GLUT-4, but not -12, in the healthy myocardium. Total GLUT4 content of the heart was decreased during diabetes, while there was no difference in total GLUT12. Active cell surface GLUT12 content was increased in the diabetic myocardium, potentially as a compensatory mechanism for the observed downregulation of GLUT4. Collectively, our data suggest that, in contrast to GLUT4, insulin does not mediate GLUT12 translocation, which may function as a basal GLUT located primarily at the cell surface in the myocardium.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Waller
authors.forename: Michael
authors.initials: M
authors.lastname: George
authors.forename: Anuradha
authors.initials: A
authors.lastname: Kalyanasundaram
authors.forename: Chen
authors.initials: C
authors.lastname: Kang
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Keli
authors.initials: K
authors.lastname: Hu
authors.forename: Véronique A
authors.initials: VA
authors.lastname: Lacombe
mesh_terms: D000818:Animals; D001692:Biological Transport; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D007328:Insulin; C498337:Slc2a12 protein, mouse; D005947:Glucose