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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
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PKCtheta is a key player in the development of insulin resistance

Deanna Haasch1, Cathleen Berg, Jill E Clampit

  • 1Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.

Biochemical and Biophysical Research Communications
|March 21, 2006
PubMed

Insights

Protein kinase C theta (PKCtheta) activation drives insulin resistance in muscle and liver. Downregulating PKCtheta protects against insulin resistance, suggesting it

Area of Science:

  • Metabolic signaling pathways
  • Cellular mechanisms of insulin resistance

Background:

  • PKCtheta activation is linked to lipid-induced insulin resistance.
  • PKCtheta knockout mice show protection against lipid-induced defects.
  • The precise mechanism of PKCtheta's contribution to insulin resistance remains unclear.

Purpose of the Study:

  • To investigate if increased PKCtheta expression causes insulin resistance.
  • To elucidate the role of PKCtheta in both muscle and liver insulin resistance.

Main Methods:

  • Overexpression of PKCtheta in C2C12 muscle cells and HepG2 liver cells.
  • Treatment with insulin, glucose, and GF-109203X (PKC inhibitor).
  • RNA interference (RNAi) to reduce PKCtheta expression.
  • Analysis of IRS-1 protein levels, p85 binding, and PKB phosphorylation.

Main Results:

  • PKCtheta overexpression reduced IRS-1 protein and impaired insulin signaling in muscle cells.
  • High insulin and glucose increased PKCtheta expression in liver cells, correlating with insulin resistance.
  • RNAi-mediated reduction of PKCtheta prevented IRS-1 degradation and improved insulin signaling.

Conclusions:

  • PKCtheta plays a critical role in the development of insulin resistance in both muscle and liver.
  • PKCtheta may contribute to whole-body insulin resistance and diabetes development.

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