胰岛素抵抗 Defronzo.ppt

* * * * * * * * Title fix in other slides ….green… and position of elements jump * * Change animation Atherosclerosis last click * Change animation Atherosclerosis last click * * * Thus, in order to further investigate the putative molecular mechanisms underlying the vascular changes that accompany the process of accelerated atherosclerosis in conditions of insulin resistance, we have developed primary cultures, as shown here under the light microscope. Initially, these cells were harvested from coronary arteries donated from our local colony of adult healthy baboons. Subsequently, we moved on to primary cultures of coronary arteries obtained from healthy adult human cadavers. You can see the spindle cell morphology typical of fibroblasts that grow into myotubules and, eventually form fully differentiated smooth muscle cells in culture. We were then ready to start working with smooth muscle cells obtained from coronary arteries of healthy adult individuals. I will limit myself to showing results from the experiments that support the clinical findings which I just discussed, namely the changes in carotid intimal media thickness and in the size of the coronary plaques detected by intravascular ultrasonography. These are shown in the next three slides ? In this slide, vascular smooth muscle cells were exposed to insulin, an insulin sensitizing agent (glitazone) and to both, and the western blot expression of the phospho-AKT, representing the PI-3 kinase insulin signaling pathway is depicted. Note that, there is a growing amount of the activated AKT component in the presence of the glitazone, and more so when insulin is added and when the two are combined. The bar graph underneath just quantifies in arbitrary units the visible changes in the gel. These data are consistent with the concept of insulin sensitization by glitazone and provide an interesting molecular mechanism. In this next slide, we show the effects of an insulin sensitizer on the p44 and p42, s