Abstract
Features of insulin binding to trophoblast plasma membranes were studied in six normal pregnant women (NP), six overt diabetes (ODP) and six poorly controlled glycemic gestational patients (PCDP) i.e. women who did not strictly follow the management of diabetes mellitus during pregnancy. A decreased maximum specific insulin receptor binding per 0.1 mg membrane protein in placenta from PCDP (12%) was found comparing with that from ODP or NP (17.5% and 36.2%, respectively, P<0.01), The insulin binding in PCDP declined at a faster rate until it reached minimum when studied at a higher temperature (25–37°C). The binding equilibrium was likewise attained faster at this temperature than that at lower temperature of 4°C for all studied groups.
The insulin receptor binding in all studied groups was pH dependent. The maximum binding in ODP and PCDP groups was attained at pH 7.8 while for NP maximum binding was at pH 7.4. The competitive dinding assay was carried out with 14 concentrations of unlabelled insulin and the half maximal displacement of125I-insulin was at 8×10−9 M, 6×10−9 M and 4×10−9 M for NP, ODP and PCDP, respectively (P<0.05) suggesting the differences in the effect of glycemic control on the insulin binding. Furthermore the binding yielded curvilinear Scatchard plots with the apparent affinity of the receptors being affected in the ODP and PCDP groups.
The molecular characteristics of the receptors in the diabetic patients as revealed by the cross-linking technique used in this study did not reveal any changes in the subunit structures when compared with normals except that the125I-insulin bound as shown by the band intensity was much less in PCDP. These findings indicate that control of hyperglycemia could optimize the outcome of insulin receptor function during diabetic pregnancy.
Similar content being viewed by others
References
Fox H: Pathology of the placenta in maternal diabetes mellitus. Obstet Gynecol 34:792–798, 1969
Coustan DR, Lewis SB: Insulin therapy for gestational diabetes. Obstet Gynecol 51:306–310, 1978
Freinkel N: The Banting lecture 1980. Of pregnancy and progeny. Diabetes 29:1023–1035, 1980
Oats JN, Beischer NA, Grant PT: The emergence of diabetes and impaired glucose tolerance in women who had gestational diabetes. In: PAM Weiss, DR Coustan (eds) Gestational Diabetes. Springer, Wien, New York, 1988, pp 199–207
Posner BI: Insulin receptors in human and animal placental tissue. Diabetes 23:209–217 1974
Nelson DM, Smith RM, Jarett L: Non uniform distribution and grouping of insulin receptors on the surface of human placental syncytial trophoblast. Diabetes 27:530–538, 1978
Harrison LC, Billington T, Clark S, Nichols R, East I, Martin FIR: Decreased binding of insulin by receptors on placental membrane from diabetic mothers. J Clin Endocrinol Metab 44:206–209, 1977
Garcia SD, Nieto JM, Cabello AM: Effect of gestational diabetes on insulin receptor in human placenta. Diabetologia 16:87–91, 1979
WHO Study Group of Diabetes Mellitus. WHO Tech Rep Ser No. 727: 10–14, 1985
Cabero L, Corcoy R, Cerquiera MJ, Condina M, Rectoret G, Baro F, De Leiva A: Treatment and outcome of 100 gestational diabetics. In: EV Gosmi, GC Di Renzo (eds) Proceedings the the XI European Congress of Perinatal Medicine. CIC Edizioni Internationali, Rome, 1988, pp 143–149.
White P: Classification of obstetric diabetes. Am J Obstet Gynecol 130: 228–230, 1978
Hofmann HMH, Weis PAM, Kainer F: Insulin treatment of gestational diabetes. The basal-bolus concept. In: PAM Weis, DR Coustan (eds) Gestational Diabetes. Springer, Wien, New York, 1988, pp 142–149
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951
Al-Attas OS: Comparative studies on the major features of insulin receptors in mammalian and non mammalian liver membranes. Comp Biochem Physiol 93B:125–133, 1989
Massague J, Czech M: The subunit structure of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptors. J Biol Chem 257:5038–5045, 1982
Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (Lond) 227:680–685, 1970
Scatchard G: The attraction of proteins for small molecules and ions. Am NY Acad Sci 51:660–670, 1949
Buse MG, Roberts WJ, Buse J: The role of the human placenta in the transfer and metabolism of insulin. J Clin Invest 41:29–41, 1962
Nelson DM, Judith ON, Curran EM: Human placental insulin binding in normal and well controlled diabetic patients. Gynecol Obstet Invest 20:1–5, 1990
Takano K, Hall L, Fryklund A, Holmgren H, Sievertsson K, Uthne K: The binding of insulin and somatostatin A to human placental membrane. Acta Endocrinol 80:14–31, 1975
Jeffrey A, Whitsett L, James L, Lessard L: Characteristics of the microvillous brush border of human placenta insulin receptor localization in brush border membrane. Endocrinology 103:1458–1468, 1978
Todd W, Siegel S, Sabyasachi G, Jacobs S, Rosen OM, Rubin CS: Purification and properties of human placental insulin receptors. J Biol Chem 256:9266–9273, 1981
Bhaumick B, Danilkewich AD, Bala RM: Altered placental insulin and insulin-like growth factors I receptors in diabetes. Life Sciences 42:1603–1614, 1988
Coustan DR, Berkowitz RL, Hobbins JC: Tight metabolic control of overt diabetes in pregnancy. Am J Med 68:845–852, 1980
Whitsett JA, Brownscheidle CM: The diabetic pregnancy: A perinatal perspective. In: IR Merkatz, PAJ Adam (eds). Grune and Stratton, New York, 1979, p 123
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Al-Attas, O.S., Al-Okail, M.S. Features of insulin receptor interaction in placenta from normal, overt and poorly controlled gestational diabetic patients. Mol Cell Biochem 126, 135–142 (1993). https://doi.org/10.1007/BF00925691
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00925691


