Abstract 17932: Diabetic Cardiomyopathy in Mice is Characterized by Defects in Myocyte Turnover Measured by Microdosing of 14C-Labeled Thymidine

Insulin-dependent diabetes mellitus was induced in mice by streptozotocin administration (175 mg/kg bw). Blood glucose was measured daily and when it reached 450 mg/dl, ~5-7 days later, 300 pCi 14C-thymidine was given intramuscularly to label forming cardiomyocytes. Control mice were similarly treated. This protocol results in a pulse labeling of replicating cells, since thymidine disappears from the circulation in less than one hour; the half-life of this nucleotide is ~15 minutes. Control and diabetic mice were sacrificed at 1, 3, 5, 10, 20, 30, 60, and 90 days after the injection of 14C-thymidine and the heart was collected. Left ventricular myocytes were isolated by enzymatic digestion, purified by differential centrifugation, and the DNA was extracted for the measurement of the kinetics of 14C concentration by Accelerator Mass Spectrometry. This is the only methodology that allows the assessment of trace-amount of 14C in the DNA. In non-diabetic control hearts, 14C concentration in the myocyte DNA in...