Insulin-receptor development in normal and diabetic pregnancies. Role of membrane fluidity.
In the hyperinsulinemic offspring of the diabetic mother, both significant macrosomia and postnatal hypoglycemia are thought to be due to increased insulin sensitivity. The purpose of this study is to characterize changes in insulin-receptor development in fetal offspring of an experimental model of diabetic pregnancy. Two groups of Sprague-Dawley female rats were studied after timed mating. Both groups received injections of either vehicle (controls) or streptozocin (diabetic), 40 mg/100 g body wt, on day 7 of pregnancy and were killed at either 17, 20, or 21 days of gestation. Maternal and fetal blood were assayed for glucose and insulin, and fetal liver membranes were prepared for 125I-labeled insulin binding, lipid composition, and fluorescence polarization studies with the probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Maternal and pooled fetal glucose levels were elevated in streptozocin-treated rats; however, pooled fetal insulin values were not elevated in the offspring of diabetic animals compared with controls (33 +/- 1 vs. 50 +/- 5 microU/ml). 125I-insulin binding was greater in fetal offspring of diabetic (FD) rat membranes at each gestational age studied [P less than .001 by analysis of variance (ANOVA)] due to significantly greater numbers of both high- and low-affinity receptors. The highest insulin-binding capacity was seen on membranes obtained from FD rats at day 21 (9.92 M X L-1 X 100 micrograms membranes-1 vs. 6.38 M X L-1 X 100 micrograms protein-1 in fetal control (FC) rats. At each gestational age, membranes from FDs had lower values for fluorescence polarization (using the probe DPH) than did gestational-age--matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002462:Cell Membrane / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D005260:Female; D005333:Fetus / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000032:analysis / Q000196:embryology; D008560:Membrane Fluidity; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000032:analysis* / Q000378:metabolism
D007328:Insulin; D011972:Receptor, Insulin