Although
sarpogrelate, a
5-HT(2A) receptor antagonist, has been reported to exert beneficial effects in diabetes, the mechanisms of its action are not understood. In this study, diabetes was induced in rats by an injection of
streptozotocin (65 mg/kg) and the animals were assessed 7 weeks later. Decreased serum
insulin as well as increased serum
glucose,
cholesterol, and
triglyceride levels in diabetic animals were associated with increased blood pressure and heart/
body weight ratio. Impaired cardiac performance in diabetic animals was evident by decreased heart rate, left ventricular developed pressure, rate of pressure development, and rate of pressure decay. Treatment of diabetic animals with
sarpogrelate (5 mg/kg) or
insulin (10 units/kg) daily for 6 weeks attenuated the observed changes in serum
insulin,
glucose, and
lipid levels as well as blood pressure and cardiac function by varying degrees.
Protein content for membrane
glucose transporters (GLUT-1 and GLUT-4) was depressed in diabetic heart; the observed alteration in GLUT-4 was partially prevented by both
sarpogrelate and
insulin, whereas that in GLUT-1 was attenuated by
sarpogrelate only. Incubation of myoblast cells with
sarpogrelate and
insulin stimulated
glucose uptake; these effects were additive.
5-hydroxytryptamine was found to inhibit
glucose-induced
insulin release from the pancreas; this effect was prevented by
sarpogrelate. These results suggest that
sarpogrelate may improve cardiac function in chronic diabetes by promoting the expression of membrane
glucose transporters as well as by releasing
insulin from the pancreas.