Adjuvant-Induced Improvement of Glucose Intolerance in Type 2 Diabetic KK-Ay Mice Through Interleukin-1 and Tumor Necrosis Factor-α

We reported that administration of complete Freundʹs adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1α and -1β antibodies or anti-tumor necrosis factor (TNF)-α antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-α.