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Insulin-induced and constitutive internalization of the insulin receptor

J L Carpentier1

  • 1Department of Morphology, University of Geneva Medical Center, Switzerland.

Hormone Research
|January 1, 1992
PubMed

Insights

Insulin receptor internalization is triggered by insulin binding and receptor kinase activity, involving redistribution to specific cell surface regions and clathrin-coated pit association. This process regulates insulin action in normal and pathological states.

Area of Science:

  • Cell biology
  • Molecular endocrinology
  • Signal transduction

Background:

  • Insulin receptor internalization is critical for understanding insulin action and regulation.
  • Definitive characterization of the receptor's intrinsic factors governing internalization is needed.
  • Understanding these mechanisms is vital for both normal physiology and pathological conditions like diabetes.

Purpose of the Study:

  • To characterize the intrinsic factors of the insulin receptor responsible for internalization.
  • To elucidate the molecular mechanisms regulating insulin receptor internalization.
  • To define the role of receptor domains and associated proteins in this process.

Main Methods:

  • Investigated receptor tyrosine kinase activity in response to insulin.
  • Analyzed receptor redistribution on the cell surface using microscopy.
  • Examined the role of specific receptor domains (juxtamembrane) in clathrin-coated pit association.

Main Results:

  • Insulin binding activates the receptor's intrinsic tyrosine kinase, initiating internalization.
  • Internalization involves receptor redistribution from microvilli to nonvillous regions.
  • A specific juxtamembrane sequence mediates ligand-independent association with clathrin-coated pits, driving constitutive internalization.

Conclusions:

  • Insulin receptor internalization is a multi-step process regulated by both ligand-dependent and independent mechanisms.
  • The tyrosine kinase activity and juxtamembrane domain are key determinants of receptor internalization.
  • These findings provide insights into insulin receptor regulation and its impact on insulin signaling.

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