Why does insulin resistance develop during maturation?

We compared skeletal muscle glucose uptake between young and mature rats. Hindlimb perfusions at insulin concentrations of 0, 100, 250, or 10,000 microU/mL were performed on male Sprague-Dawley rats at 5 weeks or 4 months of age. Basal glucose uptake, and glucose uptake at all insulin concentrations were significantly lower in the 4-month-old mature rats (p < .05). This difference was most pronounced at maximally stimulating insulin concentrations. Skeletal muscle insulin receptor binding, autophosphorylation, and tyrosine kinase activity did not differ between young and mature rats. Surprisingly, GLUT-4 glucose transporter content was significantly higher in several muscles of the mature rats (p < .05). Therefore, the decline in insulin-stimulated glucose uptake in hindlimbs of mature rats cannot be explained by decreased activity of these steps in the glucose transport system.