Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.
We reported that administration of complete Freund's 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)-1 alpha and -1 beta antibodies or anti-tumor necrosis factor (TNF)-alpha 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-alpha.
Muto
G
G
The Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, Miyagi, 980-8574, Japan.
Satoh
J
J
Muto
Y
Y
Takahashi
K
K
Nakazawa
T
T
Sagara
M
M
Miyaguchi
S
S
Fukuzawa
M
M
Qiang
X
X
Sakata
Y
Y
Takizawa
Y
Y
Li
Y
Y
Bando
S
S
Housai
T
T
Tamagawa
A
A
Toyota
T
T
D000818:Animals; D000906:Antibodies / Q000097:blood; D005122:Exudates and Transudates / Q000502:physiology; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D016219:Immunotherapy, Adoptive / Q000379:methods; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010529:Peritoneal Cavity / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant