抄録
Diabetic mice C57 BL/ksj-db/db mice are well known with their genetically obese condition. They show hyperinsulinemia and resistance to insulin from their early stage, and they soon become to disclose the same symptons as those observed in patients with maturity onset diabetes mellitus.
Using these adult models we studied changes in serum glucose and triglyceride (TG) levels by various levels of insulin, which were achieved by the daily injection of insulin or streptozotocin (STZ). Lean mice were used as a control. Three unit/kg of insulin was injected intraperitoneally to 8db/db mice and the same number of lean mice for 7 days.
Daily insulin treatment to lean mice made 53 decrease of their serum glucose levels, as compared with those in non treated lean mice. On the contrary, db/db mice whose glucose level exhibited 518±24mg/dl, did not show any change, though they were administered the same dose of insulin as lean mice.
Concomitant treatment of AS-103 (40mg/kg p.o), a derivative of ascocholorin, and insulin in 8db/db mice resulted in a statistically significant decrease of glucose level as compared with those of insulin treated control db/db mice.
On the other hand, intraperitoneal administration of STZ (180mg/kg) to db/db mice caused 29% decrease of IRI, 25% decrease of TG and in turn, 18% increase of glucose level in serum and concomitant administration of AS-103 exhibited the reduction of serum glucose, as compared with that level in STZ treated control db/db mice, indicating that endogenous insulin may work in AS-103 treated mice more effectively in the controls.
Effect of insulin on adrenaline-stimulated glycerol release was studied using epididymal fat pads slices taken from AS-103 treated and untreated db/db mice and their lean litter mates. Fat pads slices were incubated in Krebs-Ringer bicarbonte buffer containing adrenaline (1μg/ml) and insulin (10, 100, 1, 000μU/ml). Glycerol release in epididymal fat pads from db/db control mice was not affected in spite of the presence of insulin. On the other hand, the fat pads from AS-103 treated db/db mice released less glycerol than those from the non treated db/db . control mice at 100, 1, 000μU/ml of insulin.
These data may suggest that AS-103 have an effect to improve the sensitivity and responsiveness to insulin in the insulin resistant, diabetic animal model.
