GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response.

Abstract

Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM). Thus, the aims of this study were (i) to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii) to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT) women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

• Authors: Martha Lappas
• Journal: PloS one (PLoS One) Vol. 9 Issue 12 Pg. e115854 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25541965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Chir 99021
• Interleukin-1beta
• Lipopolysaccharides
• Pyridines
• Pyrimidines
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• glycogen synthase kinase 3 alpha

Topics

• Adipose Tissue (drug effects, metabolism)
• Adult
• Chemokines (metabolism)
• Diabetes, Gestational (enzymology, metabolism)
• Female
• Gene Expression Regulation, Enzymologic (drug effects)
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Inflammation (chemically induced, enzymology, metabolism)
• Intercellular Adhesion Molecule-1 (genetics)
• Interleukin-1beta (pharmacology)
• Lipopolysaccharides (pharmacology)
• Muscle, Skeletal (drug effects, metabolism)
• Obesity (complications)
• Pregnancy
• Pyridines (pharmacology)
• Pyrimidines (pharmacology)
• Vascular Cell Adhesion Molecule-1 (genetics)