The effect of in utero insulin exposure on tissue iron status in fetal rats.
Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Georgieff
M K
MK
Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis 55455.
Kassner
R J
RJ
Radmer
W J
WJ
Berard
D J
DJ
Doshi
S R
SR
Stonestreet
B S
BS
D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D007328:Insulin; D007501:Iron