Advances in the understanding of diabetic embryopathy: signal transduction.
Evidence supports the theory that in diabetic pregnant women, it is the degree of metabolic imbalance present during the crucial time of organogenesis that determines the organogenetic congenital defects. The precise mechanism responsible for abnormal fetal organogenesis is unclear, but fuels such as sugars (glucose, galactose, mannose), ketones, fuel-related principles such as somatomedin inhibitors, insulin, trace elements and, lately, myoinositol, arachidonic acid and free oxygen radicals have all been implicated. The plasma-membrane lipids, in addition to serving as barriers that separate intracellular from extracellular fluid, are the actual sources of signal molecules. In one case, the signal molecule (diphosphoinositol) is derived from a variant of a common membrane lipid. This is similar to the situation in which a hormone, or similar extracellular messenger, binds to its membrane receptor and activates an enzyme that hydrolyzes plasma-membrane phospholipids to liberate arachidonic acid, which is a precursor of signal molecules, including the prostaglandins. Disruption of these delicate processes by various agents (metabolites) could result in deficiencies in phosphoinositol turnover or arachidonic acid metabolism, thus leading to congenital anomalies.
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Department of Obstetrics and Gynecology, Beilinson Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel.
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000013:Congenital Abnormalities / Q000196:embryology / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D007294:Inositol / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D011108:Polymers; C024617:polyol; D016718:Arachidonic Acid; D007294:Inositol