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Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. Cardiovasc Diabetol 2009 Jul 31;8:43



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Pubmed Central ID




Scopus ID

2-s2.0-69549124202   28 Citations


BACKGROUND: Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.

METHODS: To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot.

RESULTS: OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21.

CONCLUSION: The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.

Author List

Reinking BE, Wedemeyer EW, Weiss RM, Segar JL, Scholz TD


Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals, Newborn
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
Diabetes Mellitus, Experimental
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases
Hypertrophy, Left Ventricular
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Pregnancy in Diabetics
Prenatal Exposure Delayed Effects
Rats, Sprague-Dawley
Remission, Spontaneous
Ventricular Remodeling
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0