Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue.

  title={Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue.},
  author={Michelle Colomiere and Michael Permezel and Martha Lappas},
  journal={Journal of molecular endocrinology},
  volume={44 4},
Severe insulin resistance is a defining attribute of gestational diabetes mellitus (GDM). It is postulated that alterations in the insulin-signalling pathway and subsequent glucose disposal are the underlying cause of insulin resistance in patients with GDM. The purpose of this study was to profile the insulin-signalling pathway and intermediates in insulin-sensitive tissues. Subcutaneous adipose tissue and skeletal muscle were collected from normal glucose-tolerant (NGT) and insulin-controlled… 

Figures and Tables from this paper

Insulin Resistance in Pregnancy Is Correlated with Decreased Insulin Receptor Gene Expression in Omental Adipose: Insulin Sensitivity and Adipose Tissue Gene Expression in Normal Pregnancy

A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance, as well as differential gene expression in omental relative to subcutaneous adipose showed a pro-insulin resistance profile.

No evidence of attenuation of placental insulin-stimulated Akt phosphorylation and amino acid transport in obesity and gestational diabetes mellitus.

It is suggested that elevated maternal insulin levels in pregnancies complicated by obesity and/or GDM promote critical placental functions, including amino acid transport, which may contribute to the increased risk of fetal overgrowth and adiposity in these pregnancies.

Activation of inflammasomes in adipose tissue of women with gestational diabetes

  • M. Lappas
  • Biology, Medicine
    Molecular and Cellular Endocrinology
  • 2014

Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

Data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis, which may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

GSK3β Is Increased in Adipose Tissue and Skeletal Muscle from Women with Gestational Diabetes Where It Regulates the Inflammatory Response

GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue.

  • M. Lappas
  • Biology, Medicine
    Metabolism: clinical and experimental
  • 2014

Double stranded viral RNA induces inflammation and insulin resistance in skeletal muscle from pregnant women in vitro.

  • M. Lappas
  • Biology, Medicine
    Metabolism: clinical and experimental
  • 2015

Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone.

Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

Data indicate that PPARγ2 is essential in promoting healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.



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

The results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity.

Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes.

Investigating the effects of pregnancy and GDM on glucose transport activity and the expression and phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1 in human skeletal muscle fiber strips in vitro indicates that impaired insulin receptor autophosphorylation is an important early distinction underlying muscle insulin resistance in young women with GDM, and it may underlie future risk for the development of type 2 diabetes.

Comparison of alterations in insulin signalling pathway in adipocytes from Type II diabetic pregnant women and women with gestational diabetes mellitus

The results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1.

Gene Expression of GLUT4 in Skeletal Muscle From Insulin-Resistant Patients With Obesity, IGT, GDM, and NIDDM

In human disease states characterized by insulin resistance, i.e., obesity, IGT, NIDDM, and GDM, GLUT4 gene expression is normal in vastus lateralis or rectus abdominis, andGLUT4 content was similar in the lean, obese, andGDM gravidas whether normalized per milligram membrane protein or per wet weight, total protein, and DNA.

Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy.

GDM women have decreased IRS-1, which may contribute to reduced insulin suppression of lipolysis with advancing gestation and may be part of the molecular mechanism to accelerate fat catabolism to meet fetal nutrient demand in late gestation.

Signaling pathways in insulin action: molecular targets of insulin resistance.

The regulation of glucose transport as the rate-limiting step in glucose utilization and storage is focused on.

Multiple Defects in the Adipocyte Glucose Transport System Cause Cellular Insulin Resistance in Gestational Diabetes: Heterogeneity in the Number and a Novel Abnormality in Subcellular Localization of GLUT4 Glucose Transporters

In GDM, insulin resistance in adipocytes involves impaired stimulation of glucose transport and arises from a heterogeneity of defects intrinsic to the glucose transport effector system, suggesting that abnormalities in cellular traffic or targeting relegate GLUT4 to a membrane compartment from which insulin cannot recruit transporters to the cell surface.

The metabolic syndrome: role of skeletal muscle metabolism.

Potential mechanisms contributing to reduced insulin signaling and action in skeletal muscle includes adipose tissue expansion and increased inflammatory adipokines, increased renin-angiotensin-aldosterone system (RAAS) activity, decreases in muscle mitochondrial oxidative capacity, increased intramuscular lipid accumulation, and increased reactive oxygen species.

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients

It is suggested that materno-fetal glucose transport increases in the placentae of women with gestational diabetes mellitus who receive insulin compared with those women who do not receive insulin.