Reduction in the Amplitude of Shortening and Ca2+ Transient by Phlorizin and Quercetin-3-O-Glucoside in Ventricular Myocytes From Streptozotocin-Induced Diabetic Rats

摘要

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64 +/- 22.23 mg/dl, n=14) than in Controls (104.06 +/- 3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76 +/- 2.91 %, n=20) and Control (83.72 +/- 2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12 +/- 2.28 %, n=20) and Control (76.69 +/- 1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37 +/- 3.16 %, n=16) and Control (73.94 +/- 5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62 +/- 5.83 %, n=18) and Control (78.32 +/- 3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.