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Updated: Jul 13, 2026
10:07
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Insulin regulates macrophage activation through activin A
Joseph Cuschieri1, Eileen Bulger, Rebecca Grinsell
1Department of Surgery, University of Washington, Seattle, Washington, USA. jcuschie@u.washington.edu
Shock (Augusta, Ga.)
|August 19, 2007
Summary
Insulin pretreatment attenuates endotoxin-induced macrophage activation by modulating the PI3K/AKT pathway and inflammatory mediator release. This effect involves activin A and SH2-containing inositol 5'-phosphatase (SHIP) regulation.
Area of Science:
- Immunology
- Cell Biology
- Endocrinology
Background:
- Strict glucose control with insulin may reduce multiple organ dysfunction syndrome by altering macrophage activation.
- The PI3K/AKT pathway is a potential mechanism for insulin's effect on macrophages.
- Understanding insulin's impact on endotoxin-mediated macrophage activation is crucial.
Purpose of the Study:
- To investigate the role of the PI3K/AKT pathway in insulin's modulation of endotoxin-activated macrophages.
- To elucidate the mechanism by which insulin affects macrophage activation.
Main Methods:
- THP-1 cells were stimulated with endotoxin after insulin pretreatment.
- Analysis of Toll-like receptor 4 signaling pathway components via immunoblot.
- Measurement of TNF-alpha and IL-8 production using ELISA.
- Assessment of transforming growth factor superfamily influence via receptor inhibition.
Main Results:
- Endotoxin activated key signaling molecules (ERK1/2, p38, JNK), degraded IkappaB, activated NF-kappaB, and increased TNF-alpha and IL-8.
- Insulin pretreatment delayed these endotoxin-induced inflammatory responses.
- Insulin increased cytoplasmic SH2-containing inositol 5 -phosphatase (SHIP) and decreased lipid raft-bound SHIP.
- Activin A blockade reversed insulin's effects on SHIP and endotoxin signaling.
Conclusions:
- Insulin regulates macrophage response to endotoxin via activin A release and SHIP production.
- Increased cytoplasmic SHIP by insulin attenuates endotoxin-mediated signaling and inflammatory mediator release.
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