Abstract

N-Glycosylation Pattern of Human Placental Insulin-Like Growth Factor and Insulin Receptors in Well-Controlled Pregestational Diabetes MellitusDiabetes mellitus is a complex disease that leads to alterations in the glycosylation of proteins. Insulin-like growth factor and insulin receptors are involved in the regulation of fetal and placental growth and development. In this work the N-glycans of these receptors, originating from placentas obtained from pregnancies complicated by pregestational insulin dependent diabetes mellitus, were studied. Diabetic mothers were under regular insulin therapy. Solubilised membrane samples from healthy and diabetic placentas were analysed using lectin-affinity chromatography. N-glycans bound to insulin-like growth factor and insulin receptors were studied in terms of their interaction with eleven agarose-immobilised lectins: wheat germ agglutinin, succinylated wheat germ agglutinin,Ricinus communisagglutinin I,Sambucus nigraagglutinin,Erythrina cristagallilectin,Ulex europaeusagglutinin,Lens culinarisagglutinin,Canavalia ensiformislectin,Phaseolus vulgariserythro- and leukoagglutinin andMaackia amurensisagglutinin. A very similar type of N-glycans and content of the terminal saccharide residues were found in both groups of placentas. The results of this work suggest that the tight glycemic control may prevent alterations in the glycosylation of insulin-like growth factor and insulin receptors, thus maintaining physiological homeostasis during pregnancy and fetal growth.

Highlights

  • The insulin-like growth factor (IGF) system is comprised of two peptides (IGF-I and IGFII), cell-surface receptors and six IGF-binding proteins [1]

  • Insulin-like growth factor and insulin receptors are involved in the regulation of fetal and placental growth and development

  • In this work the N-glycans of these receptors, originating from placentas obtained from pregnancies complicated by pregestational insulin dependent diabetes mellitus, were studied

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Summary

Introduction

The insulin-like growth factor (IGF) system is comprised of two peptides (IGF-I and IGFII), cell-surface receptors and six IGF-binding proteins [1]. IGF-I and IGF-II are involved in the regulation of various cellular processes, such as cellular growth, proliferation, differentiation, surviving against apoptosis and migration [2]. Both IGFs are believed to signal through the type 1 IGF receptor (IGF1R), IGF-II exerts some effects after its binding to the insulin receptor (IR) [3]. IGF and insulin receptors are abundantly expressed on distinct placental cell surfaces [6]. These receptors are heavily glycosylated [7]. The aim of this study was to investigate the N-glycans of IGF and insulin receptors originating from placentas of mothers with pregestational insulin dependent diabetes mellitus (IDDM)

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