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Insulin action in skeletal muscle: isozyme-specific effects of protein kinase C

Iskandar Idris1, Samuel Gray, Richard Donnelly

  • 1Division of Vascular Medicine, School of Medical and Surgical Sciences, University of Nottingham, Derbyshire Royal Infirmary, United Kingdom. is.idris@nottingham.ac.uk

Annals of the New York Academy of Sciences
|June 25, 2002
PubMed

Insights

Protein kinase C (PKC) regulates insulin signaling. Targeting specific PKC isoforms may improve insulin action and glycemic control in diabetes by addressing insulin resistance in skeletal muscle.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Protein kinase C (PKC) isozymes are crucial regulators of intracellular insulin signal transduction.
  • Skeletal muscle is a primary site for insulin-mediated glucose disposal and is sensitive to insulin resistance.
  • Understanding PKC's role in insulin resistance is vital for metabolic disease management.

Purpose of the Study:

  • To elucidate the mechanisms of PKC-induced insulin resistance in skeletal muscle.
  • To explain the seemingly contradictory roles of different PKC isoforms in insulin action.
  • To explore the therapeutic potential of targeting specific PKC isoforms for improved glycemic control.

Main Methods:

  • Review of current literature on PKC isoforms and insulin signaling pathways.
  • Analysis of the differential roles of PI3-kinase-dependent and DAG-sensitive PKC isoforms.
  • Examination of molecular mechanisms underlying insulin resistance in skeletal muscle.

Main Results:

  • Specific PKC isoforms (e.g., PKC-zeta, -lambda) act as downstream targets of PI3-kinase activation.
  • Other PKC isoforms (e.g., PKC-theta, -epsilon) exert negative regulatory effects on insulin signaling.
  • Distinct PKC isoforms mediate opposing effects on insulin action in skeletal muscle.

Conclusions:

  • The diverse functions of PKC isoforms explain their complex roles in insulin signaling.
  • Targeting specific PKC isoforms offers a potential therapeutic strategy for enhancing insulin action.
  • Pharmacological interventions aimed at PKC modulation could improve glycemic control in patients with diabetes and impaired glucose tolerance.

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