Journal of Diabetes Research

Review Article

Updating Experimental Models of Diabetic Cardiomyopathy

Table 2

Genetic models of DCM and related cardiac responses.
 UpregulationDownregulation
PPARαPPARγLCACS1LPLFATP1PKCβUCPDTACIRKOGLUT4ATGLPDK1PI3KGCK
Heart failure markers↑ANP, BNP↑ANP, BNP↑ANP, BNP↑ANP, BNP    ↑ANP, BNP  ↑ANP, BNP 
Cardiac abnormalities             
Functional              
Diastolic function↓↓↓↓↓↓↓↓↓/~↓↓↓↓
Systolic function↓↓↓↓~↓~↓↓/~↓↓~ 
Structural              
Hypertrophy↑↑↑↑↑↑↑↓↑↑↑ ↑↑
Inflammation     ↑   ~   
Fibrosis↑ ↑↑↑↑↑~↑/~↑↑↑↑
Steatosis↑↑↑↑↑  ~~↑   
Apoptosis ↑↑↑/~ ↑   ↑~↑ 
Metabolic alterations             
Glucose oxidation↓~ ↓   ↓↓/~↑↓ ↓
FA oxidation↑↑↑↑↑ ↑↓↓↓↑ ↑
Mitochondrial function↑↑↑   ↑↑ ↓ ↑↑
Oxidative stress↑↑↑    ↑↑  ↑↑
Ca2+ mobilization   ~~   ↓ ~  
References[105, 106][107, 108][109, 110][111, 112][113, 114][96][117, 118][103, 104][97–99][115, 116][100][101][102]
Genetic overexpression of PPARα, PPARγ, long-chain acyl-CoA synthetase-1 (LCACS1), lipoprotein lipase (LPL), fatty acid transport protein-1 (FATP1), PKCβ and uncoupling protein-diphtheria toxin A (UCPDTA), or ablation of cardiac-specific insulin receptor (CIRKO), GLUT4, adipose triglyceride lipase (ATGL), phosphoinositide dependent kinase-1 (PDK1), phosphoinositide-3 kinase (PI3K), and glucokinase (GCK) were forced in rodents for DCM. The associated cardiac effects and the levels of natriuretic peptides in plasma are also highlighted for each model. ↑, ↓ and ~ stand for increased, decreased, or not modified effect, respectively.