Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus

• Published in: European journal of endocrinology Vol. 160; no. 4; pp. 567 - 578
• Main Authors: Colomiere, Michelle, Permezel, Michael, Riley, Clyde, Desoye, Gernot, Lappas, Martha
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01-04-2009
• Subjects: Adult; Biological and medical sciences; Blotting, Western; C-Peptide - metabolism; Cell Membrane - metabolism; Clinical Study; Cohort Studies; Diabetes, Gestational - physiopathology; Electrophoresis, Polyacrylamide Gel; Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Humans; Immunohistochemistry; Indicators and Reagents; Insulin - physiology; Medical sciences; Obesity - complications; Obesity - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Placenta - physiopathology; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction - physiology; Vertebrates: endocrinology; Human; Pancreatic hormone; Fetal membrane; Deficiency; Maternal diseases; Insulin; Pregnancy; Signal transduction; Placenta; Complication; Female; Gestational diabetes; Woman; Endocrinology
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-09-0031

ObjectiveStudies in adipose tissue and skeletal muscle suggest that impaired insulin action is due to defects in the insulin signaling pathway and may play a role in the pathophysiology of insulin resistance associated with gestational diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that endogenous expression levels in the human term placenta of insulin signaling components are altered in placental tissue from GDM women in comparison with normal controls and maternal obesity.Design and methodsPlacental tissue was collected from normal, diet-controlled GDM, and insulin-controlled GDM in both non-obese and obese women (n=6–7 per group). Western blotting and quantitative RT-PCR was performed to determine the level of expression in the insulin signaling pathway.ResultsThere was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls. Furthermore, a decrease in both protein and mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85α and glucose transporter (GLUT)-4 was observed in non-obese and obese women with insulin controlled GDM compared with normal controls. When comparing non-obese to obese patients, significant decreases in mRNA expression of IR-β, PI3K p85α and GLUT-4 was found in obese patients.ConclusionOur results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity. In addition, expression studies demonstrate post receptor alterations in insulin signaling possibly under selective maternal regulation and not fetal regulation.