[The hypoglycemic effect of AH-9]

AH-9 is an acylhydrazine compound with hypoglycemic effects in normal mice, alloxan-induced diabetic mice and spontaneously diabetic KK mice. In terms of equi-molar doses (0.3 mmol/kg po), AH-9 was found to be more potent than phenfornin and glicalazide (diamicron) in normal mice. Insulin resistance was shown to be improved in spontaneously diabetic KK mice and hydrocortisone-induced insulin resistant mice after treatment with AH-9. The LD 50 of AH-9 given orally to mice was found to be 956 mg/kg (about 18 times its effective dose). Studies on the hypoglycemic mechanism of AH-9 (insulin release, insulin receptor and post-receptor) showed that AH-9 did not influence serum insulin levels in mice. But, in in vivo experiments, AH-9 appeared to promote the capacity and affinity of insulin receptors in mouse liver plasma membranes. AH-9 was also found to antagonize the elevation of blood glucose level and liver glycogen content caused by alanine injection. AH-9 was shown to enhance the conversion of U-14C-glucose to 14CO2 in mouse epididymal fat tissue in vitro. According to the above results, the hypoglycemic action of AH-9 might be due to: 1) increasing the capacity and affinity of insulin receptors; 2) directly enhancing glucose aerobic oxidation; and 3) inhibiting gluconeogenesis.