Cardioprotective effect of chronic hyperglycemia: effect on hypoxia-induced apoptosis and necrosis (original) (raw)

It is generally accepted that mild forms of diabetes render the heart resistant to an ischemic insult. Because myocytes incubated chronically in medium containing high concentrations of glucose (25 mM) develop into a diabetes-like phenotype, we tested the hypothesis that high-glucose treatment diminishes hypoxia-induced injury. In support of this hypothesis, we found that cardiomyocytes incubated for 3 days with medium containing 25 mM glucose showed less hypoxia-induced apoptosis and necrosis than cells exposed to medium containing 5 mM glucose (control). Indeed, whereas 27% of control cells became necrotic after 1 h of chemical hypoxia with 10 mM deoxyglucose and 5 mM amobarbital (Amytal), only 11% of the glucose-treated cells became necrotic. Similarly, glucose treatment reduced the extent of apoptosis from 32% to 12%. This beneficial effect of glucose treatment was associated with a 40% reduction in the Ca2+ content of the hypoxic cell. Glucose treatment also mediated an upregul...