TI - Substrate metabolism , insulin signaling , and cardiac efficiency . . AB - Decreased cardiac efficiency is believed to be an important contributor to the development of contractile dysfunction in type 2 diabetic models and has been postulated to result from fatty acid -induced mitochondrial uncoupling (1) . We therefore measured cardiac SUBstrate utilization and oxygen consumption in isolated working hearts of 24-week-old Akita mice in the absence and presence of insulin . Palmitate oxidation rates were increased and glucose oxidation rates were decreased in the presence or absence of 1 nmol/l insulin in Akita hearts compared with the wild type ( Fig 1D and E ) . Despite increased fatty acid oxidation , myocardial Vo2 and cardiac efficiency were not different between wild-type and Akita mice ( Fig 1G and H ) . Of interest , metabolic insulin responsiveness was retained in Akita hearts . Thus , insulin-suppressed palmitate oxidation increased glycolysis and glucose oxidation in both wild-type and Akita mice ( Fig 1D-F ) . Consistent with intact metabolic insulin signaling , insulin-stimulated Akt PHOSphorylation on Ser473 was maintained in hearts of 10 - and 24-week-old mice ( Fig 2A and B ) . Thus , despite increased fatty acid utilization , Akita hearts maintained normal insulin sensitivity .