Fig. 1.

a Sarcolemmal makeup and caveolar domains. Planar lipid rafts are more ordered elements of the sarcolemma, containing greater sphingolipid and cholesterol levels and forming signaling microdomain platforms. A subset of rafts, caveolae, localize signaling integral to ischemic tolerance and cardioprotection, including NOS, GPCRs, RTKs and coupled effector molecules. Caveolins are critical to caveolae formation and function and protective signaling. b Modulation of caveolae/caveolins and related cardioprotective signaling in DM. Diabetes may exaggerate mitochondrial dysfunction and associated death, while individual elements of DM may disrupt caveolar control and caveolin expression: (i) hyperglycemia-dependent PKCβ2 activation may suppress caveolin-3 expression/localization; (ii) saturated fats (e.g. palmitate) may displace or depress caveolin-3. Disruption of caveolar control and caveolins will limit protective signaling to mitochondria, including caveolin-3 translocation/modulation. Potential determinants of caveolin-3 expression and caveolar function include PKCβ2, saturated fats vs. n-3 PUFAs, AC (adenylate cyclase) and FAK (focal adhesion kinase) signaling, myocardin activity and physical activity