Effect of pyruvate, lactate and insulin on ATP supply and demand in unpaced perfused rat heart

Bernard Korzeniewski (1) , Veronique Deschodt-Arsac , Guillaume Calmettes , Gilles Gouspillou , Jean-Michel Franconi , Philippe Diolez

1 Faculty of Biochemistry, Biophysics and Biotechnology

Mitochondrial respiration/oxidative phosphorylation is the main source of energy in the form of ATP in heart under physiological conditions. Different respiratory substrates were used in various experiments during heart perfusion: glucose, pyruvate, lactate, glucose + pyruvate, glucose + lactate, glucose + insulin etc. Also under physiological conditions the concentration of respiratory substrates/hormones in blood can vary significantly. In the present study we tested the effect of pyruvate, lactate and insulin (all in the presence of glucose) and glucose (in the presence of pyruvate) on the ATP-producing and consuming blocks in perfused rat heart, in a system where heart rate (HR) was allowed to vary (no pacing). Changes in rate-pressure product (RPP) and phosphocreatine (PCr) concentration were measured. Proportional Activation Approach (PAA) was used to visualize and quantitatively analyze the data. It was demonstrated that addition of glucose (in the presence of pyruvate) exerted essentially no effect on the system. Insulin (in the presence of glucose) activated only the ATP producer. The most interesting finding is that in our system pyruvate and lactate (added in the presence or instead of glucose) activated ATP producer, but significantly inhibited ATP consumer (their effect was quantitatively identical).

Mots clés: Life Sciences

Bernard Korzeniewski, Veronique Deschodt-Arsac, Guillaume Calmettes, Gilles Gouspillou, Jean-Michel Franconi, et al.. Effect of pyruvate, lactate and insulin on ATP supply and demand in unpaced perfused rat heart. Biochemical Journal, 2009, 423 (3), pp.421-428. ⟨10.1042/BJ20090395⟩. ⟨hal-00479172⟩