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Why does insulin resistance develop during maturation?

M J Reed1, G M Reaven, C E Mondon

  • 1Department of Medicine, Stanford University School of Medicine, California.

Journal of Gerontology
|July 1, 1993
PubMed
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Mature rats show reduced skeletal muscle glucose uptake compared to young rats, despite normal insulin receptor function. This suggests age-related metabolic changes affect glucose transport beyond initial insulin signaling pathways.

Area of Science:

  • Physiology
  • Metabolism
  • Endocrinology

Background:

  • Insulin is a key hormone regulating glucose uptake in skeletal muscle.
  • Age-related changes in insulin sensitivity can impact metabolic health.

Purpose of the Study:

  • To compare skeletal muscle glucose uptake between young and mature rats.
  • To investigate the underlying mechanisms for potential age-related differences in insulin-stimulated glucose uptake.

Main Methods:

  • Hindlimb perfusions were conducted on young (5-week-old) and mature (4-month-old) male Sprague-Dawley rats.
  • Glucose uptake was measured at various insulin concentrations (0-10,000 microU/mL).
  • Insulin receptor binding, autophosphorylation, tyrosine kinase activity, and GLUT-4 transporter content were assessed.

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Main Results:

  • Mature rats exhibited significantly lower basal and insulin-stimulated glucose uptake in hindlimbs compared to young rats.
  • These differences were most pronounced at maximal insulin concentrations.
  • No significant differences were observed in skeletal muscle insulin receptor binding, autophosphorylation, or tyrosine kinase activity between age groups.
  • Interestingly, GLUT-4 glucose transporter content was higher in several muscles of mature rats.

Conclusions:

  • The reduced insulin-stimulated glucose uptake in mature rats is not attributable to defects in insulin receptor signaling or reduced GLUT-4 expression.
  • Age-related impairments in skeletal muscle glucose uptake involve post-GLUT-4 translocation steps in the glucose transport system.