[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.
Jiang
Z
Z
Institute of Materia Medica, CAMS and PUMC, Beijing.
Xie
M
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D006834:Hydrazines / Q000378:metabolism* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011972:Receptor, Insulin / Q000187:drug effects
D001786:Blood Glucose; D006834:Hydrazines; D007004:Hypoglycemic Agents; D008112:Liver Glycogen; C087065:AH 9; D011972:Receptor, Insulin