Hypoglycemia and embryonic heart development.
Abnormal embryonic development is a complication of the diabetic pregnancy, and heart defects are among the most common and detrimental congenital malformations of the diabetic embryopathy. Hypoglycemia is a common side effect of diabetes therapy and is a potential teratogen. An association between hypoglycemia and congenital defects has been difficult to demonstrate in humans, but in vivo and in vitro animal studies have illustrated the importance of glucose as a substrate for normal development. Hypoglycemia alters embryonic heart morphology, producing abnormal looping and chamber expansion, decreased myocardial thickness, disorganized layers, and decreased overall size. Hypoglycemia decreases embryonic heart rate and vascularity, and it alters embryonic heart metabolism by increasing glucose uptake and glycolysis. Hypoglycemia also affects protein expression in the embryonic heart, increasing the expression of glucose regulated proteins, hexokinase, and glucose transport protein. Thus, hypoglycemia interferes with normal cardiogenesis and alters morphology, function, metabolism, and expression of certain proteins in the developing heart. It is likely that these factors contribute to heart defects observed in the diabetic embryopathy, but the definitive link has yet to be made. Future studies are expected to further elucidate mechanisms mediating hypoglycemia-induced cardiac dysmorphogenesis.
Smoak
Ida W
IW
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. ida_smoak@ncsu.edu
D000818:Animals; D005314:Embryonic and Fetal Development; D005260:Female; D005318:Fetal Heart / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000503:physiopathology; D006801:Humans; D007003:Hypoglycemia / Q000196:embryology* / Q000503:physiopathology*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000196:embryology* / Q000503:physiopathology*