Beneficial effects of certain phosphodiesterase inhibitors on diabetes mellitus in rats

Abstract

The present study is conducted to investigate the possible antidiabetic effect of certain phosphodiesterase inhibitors. Diabetes mellitus was induced in 18h-fasted male wistar albino rats by intraperitoneal injection of streptozotocin (STZ) in a single dose (50mg/kg). Gliclazide (Glcl) as a reference standard in a dose of 10mg/kg, sildenafil (Sild) in 3 doses (5, 10, 20mg/kg) as PDE5 inhibitor and vinpocetine (Vinp) in 3 doses (10, 20, 40mg/kg) as PDE1 inhibitor were injected intraperitoneal daily for 2weeks. Their effects were assessed at different time intervals namely; 2h after first dose, 1week and 2weeks after drug administration. In the present study, STZ significantly elevated serum blood glucose (SBG) level, lowered serum insulin, C-peptide levels and decreased liver glycogen content (LGC). Glcl significantly elevated serum insulin and C-peptide levels accompanied by reduction in serum glucose level and raised LGC. Vinp and Sild elevated serum insulin, C-peptide levels, LGC and decreased SBG level. The antidiabetic effect of Glcl was significantly higher than that of Vinp or Sild. It could be concluded that Vinp possibly produced its insulin stimulatory action via inhibition of PDE1 while Sild stimulated insulin secretion through inhibition of PDE5. The increase in serum C-peptide indicated that Vinp and Sild stimulated synthesis of insulin in the β-cells and Vinp is more potent than Sild in this respect due to the difference in their mechanism of action.