title: Insulin-receptor kinase is enhanced in placentas from non-insulin-dependent diabetic women with large-for-gestational-age babies.
abstract: The function of insulin receptor and IGF-1 receptor was investigated in placentas from 10 healthy control mothers, 8 diabetic mothers with appropriate-for-gestational-age babies (AGA group) and 9 diabetic mothers with large-for-gestational-age babies (LGA group). None of the diabetic mothers were obese before pregnancy; their blood glucose was well controlled during pregnancy and glycosylated HbA1c was 6.52 +/- 0.71% (M +/- S.E.). Insulin and IGF-1 receptors were partially purified from placentas using wheat germ agglutinin chromatography. The insulin-binding capacity was significantly increased in both the AGA and the LGA groups compared to the control, whereas the IGF-1 binding capacity was similar in the three groups. Autophosphorylation studies were performed with partially purified receptors equalized for similar binding capacity, then immunoprecipitated with anti-insulin receptor antibody or anti-IGF-1 receptor antibody. Insulin-stimulated 32P-incorporation into the insulin receptor beta-subunit was increased by 133% in the LGA group versus the control, whereas incorporation in the AGA group was equivalent to the control. Insulin-stimulated tyrosine kinase activity of the receptor preparation for histone H2B phosphorylation was also significantly increased in the LGA group compared to the control. 32P-incorporation into beta-subunit IGF-1 receptor and IGF-1-stimulated tyrosine kinase activity did not show any significant differences among the three groups. The data in the present study suggest that elevated insulin receptor kinase might be involved in fetal overgrowth in diabetic mothers.
authors.affiliation: Diabetes Center, Tokyo Women's Medical College, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takayama-Hasumi
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: M
authors.initials: M
authors.lastname: Shimisu
authors.forename: S
authors.initials: S
authors.lastname: Minei
authors.forename: M
authors.initials: M
authors.lastname: Sanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Omori
mesh_terms: D000328:Adult; D001724:Birth Weight; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D010766:Phosphorylation; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000302:isolation & purification / Q000378:metabolism; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D012016:Reference Values
chemical_list: D007328:Insulin; D007457:Iodine Radioisotopes; C008147:insulin, iodo-; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin