REGULATION OF GLUCOSE TRANSPORT IN THE ISCHEMIC HEART

Yale University, New Haven CT

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Abstract

DESCRIPTION (adapted from the applicant's description): Ischemia produces translocation of the glucose transport proteins GLUT4 and GLUT1 to the sarcolemma as a critical response to a need for energy. This study proposes to understand the mechanism of this response by using rat papillary muscle in combination with pharmacological tools and an in vivo model of canine ischemia. The hypothesis to be tested is that ischemia triggers activation of AMP kinase, an intracellular protein that is proposed to increase glucose transporters on the sarcolemma. Interaction of AMPK with other signaling pathways will be explored, as well as the role of specific isoforms of AMPK subunits in the heart. The relative roles of exocytosis vs. endocytosis in the process will be evaluated.