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Published on: July 30, 2014
Involvement of the actin network in insulin signalling
1Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Society of General Physiologists Series
|January 1, 1997
Summary
The actin network is crucial for insulin to stimulate glucose transport and activate Erk MAPKs. Disrupting actin prevents glucose transporter movement and MAPK activation, though PI 3-kinase activation remains unaffected.
Area of Science:
- Cellular biology
- Molecular signaling
- Metabolic regulation
Background:
- Insulin signaling involves complex cascades regulating glucose transport and cell growth.
- The actin cytoskeleton plays a role in cellular processes, but its specific involvement in insulin action is not fully understood.
- Key pathways include insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinases (MAPKs).
Purpose of the Study:
- To investigate the role of the actin network in insulin-stimulated glucose transport.
- To examine the actin network's function in the activation of the Erk mitogen-activated protein kinase (MAPK) cascade.
- To determine if actin disassembly affects early insulin signaling events like IRS-1 phosphorylation and PI 3-kinase activation.
Main Methods:
- Used cytochalasin D, a fungal metabolite, to disassemble the actin network in L6 muscle cells and 3T3-L1 adipocytes.
- Assessed insulin-stimulated glucose transport rates.
- Measured insulin-mediated phosphorylation of IRS-1, PI 3-kinase association and activation, and Erk MAPK phosphorylation.
Main Results:
- Actin disassembly completely inhibited insulin-stimulated glucose transport by preventing glucose transporter recruitment to the plasma membrane.
- Actin disassembly did not affect insulin-induced IRS-1 phosphorylation or PI 3-kinase activation.
- Actin disassembly abolished insulin-mediated Erk MAPK phosphorylation, while PI 3-kinase recruitment to intracellular membranes was inhibited in adipocytes.
Conclusions:
- The actin network is essential for insulin-stimulated glucose transport and Erk MAPK activation.
- Actin disassembly does not impede initial insulin signaling (IRS-1, PI 3-kinase activation) but prevents downstream propagation.
- Intact actin filaments are required for the cellular redistribution of signaling molecules and the activation of MAPKs in response to insulin.
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