Insulin resistance of adjuvant-induced granuloma pouch formation in genetically diabetic KK-CAy mice.

The characteristics of adjuvant-induced pouch granuloma in genetically diabetic KK-CAy mice with hyperinsulinemia were investigated. Both the dose-response relationship and the time-course experiments showed that the wet weight of pouch granuloma in diabetic KK-CAy mice was lower than in ddY normal mice. Insulin treatment enhanced granuloma formation in KK-CAy mice, and it restored the suppressed DNA content in the granuloma tissue to the level in ddY mice. Although the DNA content was dose-dependently increased by insulin, the ratio of DNA content to granuloma weight was constant. In severely diabetic mice, the granuloma weight was not different from that in normoglycemic mice, despite significantly higher blood insulin levels and greater body weight. Insulin stimulated granuloma formation in severely diabetic KK-CAy mice only when higher doses (1 mg/kg) were given. This evidence suggests that suppression of granuloma formation in diabetic KK-CAy mice is due to insulin resistance and that restoration requires pharmacological doses of insulin.