Effects of insulin and hydrostatic forces on the metabolism of the aorta.

To better understand the putative association between insulin and atherosclerosis many experimental studies have explored the metabolic effects of insulin upon the arterial intima-media (which is essentially made up of smooth muscle cells). This tissue appears to be insulin-sensitive in vivo but not in vitro, suggesting that the actions of insulin on arterial metabolism are probably indirect. Yet, cultured arterial smooth muscle cells do increase their anabolism when physiological concentrations of insulin (10-250 microU/ml) are added to the medium. To account for these discrepancies we have proposed a haemodynamic explanation : hydrostatic forces present in vivo but absent in vitro, would be necessary for insulin to reach the cells of the media and act upon them. We demonstrated such an effect using an isolated rat aorta perfused under variable pressure. But only highly unphysiological concentrations of insulin (0.1 mU/ml) could stimulate the metabolism of intima-media significantly. The insulin-sensitivity of the target tissue for atherosclerosis remains an enigma. We speculate that the variable phenotype of arterial smooth muscle cells (either contractile or synthetic) might be an interesting clue to this problem.