title: Proposed regulation of gene expression by glucose in rodent heart.
abstract: BACKGROUND
  During pressure overload-induced hypertrophy, unloading-induced atrophy, and diabetes mellitus, the heart induces 'fetal' genes (e.g. myosin heavy chain beta; mhc beta).
  
  
  OBJECTIVE
  We propose that altered glucose homeostasis within the cardiomyocyte acts as a central mechanism for the regulation of gene expression in response to environmental stresses. The evidence is as follows.
  
  
  RESULTS
  Forced glucose uptake both ex vivo and in vivo results in mhc isoform switching. Restricting dietary glucose prevents mhc isoform switching in hearts of both GLUT1-Tg mice and rats subjected to pressure overload-induced hypertrophy. Thus, glucose availability correlates with mhc isoform switching under all conditions investigated. A potential mechanism by which glucose affects gene expression is through O-linked glycosylation of specific transcription factors. Glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the flux generating step in UDP-N-acetylglucosamine biosynthesis, the rate determining metabolite in protein glycosylation. Ascending aortic constriction increased intracellular levels of UDP-N-acetylglucosamine, and the expression of gfat2, but not gfat1, in the rat heart.
  
  
  CONCLUSIONS
  Collectively, the results strongly suggest glucose-regulated gene expression in the heart, and the involvement of glucose metabolites in isoform switching of sarcomeric proteins characteristic for the fetal gene program.
authors: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.
authors: Martin E
authors: ME
authors: Young
authors: Jie
authors: J
authors: Yan
authors: Peter
authors: P
authors: Razeghi
authors: Robert C
authors: RC
authors: Cooksey
authors: Patrick H
authors: PH
authors: Guthrie
authors: Stanislaw M
authors: SM
authors: Stepkowski
authors: Donald A
authors: DA
authors: McClain
authors: Rong
authors: R
authors: Tian
authors: Heinrich
authors: H
authors: Taegtmeyer