Effects of pioglitazone on ventricular myocyte shortening and Ca²⁺ transport in the goto-kakizaki type 2 diabetic rat

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca²⁺ current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 μM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 μM PIO reduced the amplitude of the Ca²⁺ transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca²⁺ release from the sarcoplasmic reticulum and recovery of Ca²⁺ transients following application of caffeine and myofilament sensitivity to Ca²⁺ were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca²⁺ current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca²⁺ transient however, the mechanisms remain to be resolved.