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Alteration of insulin receptor kinase in obese, insulin-resistant mice

T Gremeaux1, J F Tanti, E Van Obberghen

  • 1INSERM U145, Faculté de Médecine (Pasteur), Nice, France.

Biochimie
|April 1, 1987
PubMed

Insights

Obese mice show reduced insulin receptor kinase activity, not just fewer receptors. This defect in insulin signaling may stem from impaired message transmission or enzyme function.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Obesity is linked to insulin resistance, a condition where the body doesn't respond effectively to insulin.
  • Muscle insulin receptors play a crucial role in glucose uptake and metabolism.
  • Understanding defects in insulin receptor function is key to addressing insulin resistance.

Purpose of the Study:

  • To investigate the properties of muscle insulin receptors in obese mice.
  • To compare insulin receptor number, binding affinity, and kinase activity between lean and obese mice.
  • To identify potential defects in insulin receptor function contributing to insulin resistance.

Main Methods:

  • Partial purification of insulin receptors using wheat germ agglutinin--agarose chromatography.
  • Assessment of receptor autophosphorylation and substrate phosphorylation (glutamate--tyrosine copolymer).
  • Analysis of phosphopeptides using High-Performance Liquid Chromatography (HPLC).

Main Results:

  • Obese mice had a 25% decrease in muscle insulin receptor number, with no change in binding affinity.
  • Insulin receptor kinase activity was diminished in obese mice to a greater extent than the receptor number reduction.
  • HPLC analysis showed identical phosphopeptide patterns, suggesting the defect is not in the primary phosphorylation sites.
  • Trypsin treatment was less effective in stimulating kinase activity in obese mice, indicating altered enzyme function or signaling.

Conclusions:

  • The study suggests a defect in insulin receptor kinase activity in obese mice.
  • This defect may involve impaired signal transmission from the alpha- to beta-subunit of the receptor.
  • Alternatively, environmental conditions might impair the enzyme's functioning in obese individuals.

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