Augmentation of the inotropic response to insulin in diabetic rat hearts

Insulin participates in the modulation of myocardial function, but its inot ropic action in diabetes mellitus is not fully clear. In the present study, we examined contractile responses to insulin in left-ventricular papillary muscles and ventricular myocytes isolated from hearts of normal or short-t erm (5-7 days) streptozotocin-induced (65 mg/kg) diabetic rats. Mechanical properties of papillary muscles and ventricular myocytes were evaluated usi ng a force transducer and an edge-detector, respectively. Contractile prope rties of papillary muscles or cardiac myocytes, electrically stimulated at 0.5 Hz, were analyzed in terms of peak tension development (PTD) or peak tw itch amplitude (PTA), time-to-peak contraction (TPT) and time-to-90% relaxa tion (RT90). Intracellular Ca2+ transients were measured as fura-2 fluoresc ence intensity change (Delta FFI). Insulin (1-500 nM) had no effect on PTD in normal myocardium, whereas it produced a positive inotropic response in preparations From diabetic animals, with a maximal increase of 11%. Insulin did not modify TPT or RT90 in either group. Further studies revealed that insulin enhanced cell shortening in diabetic but not normal myocytes, with a maximal increase of 21%. Consistent with its action on the mechanical pro perties of papillary muscles and cardiac myocytes, insulin also induced a d ose-dependent increase in the intracellular Ca2+ transient in diabetic but not normal myocytes. Collectively, these data suggest that the myocardial c ontractile response to insulin may be altered in diabetes.