Proapoptotic and antiapoptotic effects of hyperglycemia: role of insulin signaling.

摘要: Glucose toxicity is an important initiator of cardiovascular disease, contributing to the development insulin resistance, impaired contractile function, abnormal energy metabolism, cardiomyocyte and endothelial cell death, coronary heart failure. High blood glucose can, however, paradoxically protect against a variety insults, including ischemia, hypoxia, calcium overload. To provide information on underlying basis these divergent actions high glucose, present study examined hypothesis that adverse effects are linked signaling, leading reduction in levels cytoprotective factors, beneficial occur absence result improvement Akt signaling. This was evaluated by using vitro model amenable manipulations insulin. Prolonged exposure isolated neonatal medium containing led increased susceptibility angiotensin II-mediated apoptosis, effect associated with reduced phospho-Akt Bax/Bcl-2 ratio. By contrast, rendered resistant apoptosis. Because were elevations Bcl-2 content, cardioprotective activity resembles Hence, activation state largely determined other growth factors. diminishes it reduces renders susceptible damaging insults. In insulin, natural unmasked. As result, signaling death.