Age dependent changes of insulin receptors in rat tissues

Aging is associated with insulin resistance but the exact molecular mechanism is still unknown. Tissue insulin resistance can be evoked by the decreased sensitivity to insulin, the decreased responsiveness to hormone or both. As the first step in insulin action is its binding to alfa subunits of the receptor we, therefore, studied the insulin binding kinetics in plasma membranes of the liver, heart and skeletal muscle in order to establish whether their ability to bind the hormone is altered with aging. Plasma membranes were prepared and purified according to Havrankowa and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters of the hormone-receptor interaction were analysed by the method of Scatchard using the LIGAND-Pc v.3.1. computer program. The binding potency of insulin was calculated as IC50 using ALLFIT-Pc v.2.7. computer program. We have shown that there are striking differences in insulin binding kinetics in newborn and old rats, depending on kind of tissue tested. The liver plasma membranes ability for insulin binding, number of high (HAIR) and low (LAIR) affinity insulin receptors, values of the dissociation constants and products of association constants and number of insulin receptors, were almost the same, being not dependent on age of the rats. By contrast, there is less high affinity insulin receptors in skeletal muscle of the old animals. The most dramatic changes in insulin binding occur in the heart where both high and low affinity insulin receptors are greatly affected by aging. Our results indicate that the response of the three tissues tested to hyperglycemia and hyperinsulinemia, observed in the old rats, has not been identical and probably can be accounted for by the different distribution of insulin receptor isoforms in the liver, heart and skeletal muscles as shown recently by Vidal et al.