Type 1 diabetes (TOD) increases the risk of coronary artery disease and 
myocardial infarction and is characterized by baseline cardiac dysfunction. We 
investigated the influence of TOD in post-infarct remodeling (REM) and the role 
of thyroid hormone (TH) signaling in this response. Acute myocardial infarction 
(AMI) was induced in rats with type I diabetes (TOD) and in non diabetic rats 
(NTOD-AMI), sham-operated rats serving as controls (SHAM). AMI resulted in 
tissue hypothyroidism due to significant downregulation of the TH receptors TRa1 
and TRbeta1 in the TOD myocardium, while no change in plasma T3 or T4 was 
observed This response was associated with increased expression of beta-MHC and 
distinct changes in cardiac function and geometry: EF % was decreased in TOD-AMI 
as compared to NTOD-AMI. Systolic and diastolic chamber dimensions were 
increased, with no concomitant increase in wall thickness. Thus, WTI (the ratio 
of LVIDd/2 x posterior wall thickness), an index of wall stress, was 
significantly increased in TOD-AMI. The absence of wall thickening in TOD-AMI 
hearts was associated with changes in stretch-induced kinase hypertrophic 
signaling: phosporylated (p) ERK and p-p38 MAPK levels were not changed in 
TOD-AMI in comparison with non infarcted hearts (TOD-SHAM) and NTOD-A MI hearts. 
TH administration after AMI prevented tissue hypothyroidism and resulted in 
decreased beta-MHC expression, increased wall thickening and normalized 
wallstress, while stretch-induced p38 MAPK activation was increased. We conclude 
that diabetes exacerbates post-ischemic cardiac remodeling and that tissue 
hypothyroidism may be involved in this response.