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Volume 14 Supplement 2

Sepsis 2010

Lipopolysaccharide alters expression of incretin receptors in monocytic and hepatocytic cell lines

Introduction

Sepsis hyperglycemia is poorly understood. It is not known whether there is a role in sepsis hyperglycemia for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), crucial for normal glucose metabolism. We developed an in vitro model of sepsis employing monocytes (crucial cells in mediating sepsis) and hepatocytes (crucial cells in carbohydrate homeostasis) to clarify the role of the incretin system in sepsis.

Objective

To establish an in vitromodel of sepsis employing monocytic (U937) and hepatocytic (HUH7) cell lines by co-incubation with lipopolysaccharide (LPS) and to determine whether receptor expression for GIP, GLP-1, and insulin (INS) was altered.

Methods

U937 (monocyte cell line) and HUH7 (hepatocyte cell line) cells were cultured with different concentrations of LPS for 24 hours. Real-time RT-PCR quantitation of gene expression was used to compare the rates for relative expression.

Results

U937 and HUH7 cells expressed mRNA GIPR (including GIPR protein expression in HUH7 cells), and INSR, but only HUH7 expressed GLP-1R. There was an inverse relationship between the LPS dose and mRNA expression for GIPR (P < 0.05). For example at 5 μg/ml LPS, the expression of GIPR was reduced to 86% and INSR 72% of control in U937: while in HUH7 cells at 1 μg/ml LPS, the GIPR expression was decreased to 63%, GLP-1R 95% and INSR 89% compared with control (P < 0.001). A direct significant relationship between LPS and inflammatory cytokines IL-1 (P < 0.05) and IL-6 (P < 0.05) in both cell lines validated our model.

Conclusions

We not only show for the first time GIPR mRNA expression on U937 cells and expression of GIPR and GLP-1R on hepatocyte cell line, but also their downregulation with LPS. The LPS-mediated alteration in incretin receptor expression on these cell lines may be relevant to changes in cytokine secretion and carbohydrate metabolism in sepsis.

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Correspondence to H Daabo.

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Daabo, H., Welters, I., Gallagher, J. et al. Lipopolysaccharide alters expression of incretin receptors in monocytic and hepatocytic cell lines. Crit Care 14, P18 (2010). https://doi.org/10.1186/cc9121

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Keywords

  • Receptor Expression
  • U937 Cell
  • HUH7 Cell
  • Monocyte Cell
  • Hepatocyte Cell Line
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