Abstract: OBJECTIVE: To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-soluble fraction of bee venom(BWCBVA) drug over orally administered bee wax(BW) and intraperitoneally administered whole bee venom(BV) in streptozotocin(STZ)-induced diabetic rats.METHODS: Diabetes induced by intraperitoneal administration of 60 mg/kg STZ was treated with BWCBVA, BW, and BV for 21 d. The biochemical, protein and histological changes, and physical characteristics of BWCBVA were then analyzed.RESULTS: The BWCBVA group shows significantly decreased blood glucose level as compared to the BW and intraperitoneally administered whole BV treated group. Moreover, BWCBVA significantly normalizes the serum biochemical parameters and increases the body weight. Also, administration of BWCBVA significantly reverses the altered liver expression of phosphatidylinositide 3-kinases-p85 and liver glucokinase. Histological analysis of the pancreas an increase in the islet cell numbers and decrease in β-cell damage. Co-administering BWCBVA 0.25 mg/kg with nifedipine(6.8 mg/kg) and nicorandil(13.8 mg/kg) to the diabetic rats results in insulin secretion through enhanced calcium ion influx. High performance liquid chromatography and gas chromatography was performed to identify the pharmacologically important compounds present in BWCBVA.CONCLUSION: Our results indicate that BWCBVA,an orally administered colon specific drug delivery system, can be effective in treating diabetes mellitus.

Key words: Diabetes Mellitus, Waxes, Bee venoms, Streptozotocin