The Role of Phospholipid Metabolism in Insulin Action

  • Robert V. Farese
  • Denise R. Cooper


There are two major mechanisms whereby hormones and other agonists alter phospholipid metabolism and generate intracellular signaling substances in their respective target tissues, viz., phospholipase activation and phospholipid synthesis. The most widely popularized mechanism involves the activation of a specific phospholipase C which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2).1 This hydrolysis generates inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which, respectively, mobilize Ca++ from intracellular stores and activate protein kinase C2 and other possibly related kinases. This hydrolytic mechanism is probably operative in the action of most agonists which operate via cell surface receptors and use Ca++ as a major intracellular signaling substance. In addition to PIP2 hydrolysis, other types of phospholipase C may be activated, causing the hydrolysis of phosphatidylcholine (PC),3 phosphatidylinositol (PI) or a PI-glucosamine complex (PI-glycan).4 While it is clear that cell surface receptors are coupled to the PIP2 phospholipase C through GTP-binding proteins (which may or may not be inhibited by pertussis toxin), little is known about the mechanisms whereby receptors activate other forms of phospholipase C.


Glucose Transport Insulin Action Insulin Treatment Phosphatidic Acid Phorbol Ester 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Robert V. Farese
    • 1
  • Denise R. Cooper
    • 1
  1. 1.University of South Florida College of Medicine and J. A. Haley Veterans HospitalTampaUSA

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