Dietary vitamin and lipid therapy rescues aberrant signaling and apoptosis and prevents hyperglycemia-induced diabetic embryopathy in rats.
OBJECTIVE
Maternal diabetes causes developmental malformations in the embryo. Dietary supplementation with antioxidants can reduce the malformation rates in animal models. To investigate the molecular mechanisms underlying diabetes-induced embryonic abnormalities and dietary interventions, activity of mitogen-activated protein kinases and factors associated with apoptotic pathways were examined in the maternal diabetic rat model.


METHODS
Diabetes was induced in pregnant rats using streptozotocin. In the yolk sacs of the embryos, activity of the extracellular signal-regulated kinases, Raf-1, and Akt was dramatically reduced in diabetic rats, whereas that of c-jun N-terminal kinases/stress-activated protein kinases was increased.


RESULTS
When the diabetic dams were fed with arachidonic acid, vitamin E, or a combination of arachidonic acid, vitamin E, and myoinositol, the changes in the expression of these kinases were reversed and correlated with the decreases in the rates of apoptosis and embryonic malformations.


CONCLUSIONS
These results suggest that mitogen-activated protein kinases are involved in diabetic embryopathy, and dietary supplementations can rescue the aberrant signaling pathways and reduce embryonic malformation rate.
Reece
E Albert
EA
Department of Obstetrics and Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA. reeceealbert@uams.edu
Wu
Ying-King
YK
Zhao
Zhiyong
Z
Dhanasekaran
Danny
D
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D053938:DNA Fragmentation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D014810:Vitamin E; D016718:Arachidonic Acid; D020928:Mitogen-Activated Protein Kinases