Effect of Ascochlorin Derivative AS-6 on Calcium Metabolism of Genetically Diabetic db/db Mice

Abstract

The effect of the Ascochlorin derivative AS-6, a new hypoglycemic agent, on calcium metabolism was studied in genetically obese diabetic mice, C₅₇Bl/ksj-db/db (db/db). Sixteen male db/db mice and seven lean littermates were used. The db/db mice were allocated to two groups (n=8), one of which was fed a commercial chow (Nihon CLEA, CE-2) as was the lean group. The other db/db group was fed CE-2 chow containing 0.1% AS-6 for 10 days. Serum glucose levels in thed b/db controls showed significant (p<0.01) increases of 3.4 times as compared with the lean controls mice. When AS-6 was given, serum glucose was reduced by 23% as compared with the db/db controls mice. Urinary Ca excretion in db/db controls (30.9 ± 8.2 μg/day) was significantly (p<0.01) higher than in the lean controls (6.8 ± 0.6). AS-6 reduced urinary Ca levels by 61%. Urine Ca levels were correlated to serum glucose (r=0.727) and to urine glucose (r=0.910). Serum Ca levels in db/db controls were significantly (p<0.01) higher than in the lean controls (12.63 ± 0.22 vs. 11.63 ± 0.25 mg/dl). AS-6 significantly (p<0.01) reduced serum Ca levels by 9% as compared with the db/db controls. Serum insulin and calcitonin levels in db/db controls were 15.6 times and 6.6 times, respectively, the levels in the lean controls. AS-6 decreased calcitonin levels by 56% as compared with the db/db controls. There was a correlation between serum calcium and insulin in db/db treated with AS-6 or not (r=0.666). The results showed that db/db mice required much insulin release for blood glucose to decrease, that hyperinsulinemia may contribute to increased serum calcium levels, and that potentiation of insulin action by AS-6 lessens hyperglycemia and hypercalcemia in db/db mice.