Lack of teratogenic effect of brief maternal insulin-induced hypoglycemia in rats during late neurulation.
We have previously shown that 1 h of maternal insulin-induced hypoglycemia is teratogenic to rat embryos during the initial stages of neurulation, when they are dependent on uninterrupted glycolysis (day 9.5-9.7 of development). To determine whether this vulnerability persists in later stages of neural tube and cardiac development, we infused insulin into 16 conscious pregnant rats for 1 h beginning after embryos had developed the capacity for aerobic glucose metabolism (day 10.6 of development). Half of the pregnant animals were allowed to become hypoglycemic (44 +/- 2 mg/dl) during the insulin infusions. The other half received glucose infusions to maintain normoglycemia (130 +/- 3 mg/dl). Normal plasma glucose levels were maintained in all animals after the insulin infusions. Embryos were examined on day 11.5 of development. At that time, 1 of 111 embryos from the normoglycemic group and 1 of 109 embryos from the hypoglycemic group were grossly malformed (P greater than .5). Means of embryo crown-rump length (4.15 +/- 0.03 vs. 4.14 +/- 0.03 mm), somite number (29.7 +/- 0.1 vs. 29.8 +/- 0.2), and total protein content (320 +/- 5 vs. 326 +/- 6 micrograms) were also similar in the two groups (P greater than .5). Thus, we could not detect an embryotoxic effect of 1 h of maternal insulin-induced hypoglycemia beginning at day 10.6 of development. This finding is in contrast to our prior demonstration that a similar period of hypoglycemia occurring earlier in neurulation (day 9.7) caused growth retardation and developmental anomalies in embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
Buchanan
T A
TA
Department of Medicine, University of Southern California Medical School, Los Angeles.
Sipos
G F
GF
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications*; D007328:Insulin / Q000633:toxicity*; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin