Spleen-Derived Anti-Inflammatory Cytokine IL-10 Stimulated by Adipose Tissue-Derived Stem Cells Protects Against Type 2 Diabetes.
Considering that the spleen plays an important role in the occurrence and development of diabetes, we aimed at investigating the role of the spleen in the treatment of type 2 diabetes (T2D) with adipose tissue-derived stem cells (ADSCs). We established a T2D/splenectomy (SPX) rat model by using high-fat diet/streptozotocin administration with SPX, assessed the therapeutic effects of ADSCs, and explored the possible mechanism. A single ADSC infusion was found to ameliorate hyperglycemia and insulin resistance in diabetic rats, accompanied by a considerable number of ADSCs homing to the spleens in T2D rats. Moreover, four times of infusion of ADSCs resulted in a more significant reduction of blood glucose and insulin resistance, whereas SPX exacerbated hyperglycemia and insulin resistance and attenuated the effects of ADSCs. In addition, ADSC infusion promoted anti-inflammatory cytokine interleukin (IL)-10 expression and inhibited pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor (TNF)-α expression in both the spleen and serum of T2D rats without SPX. ADSCs also inhibited serum IL-6, IL-1β, and TNF-α expression, but cannot promote IL-10 expression in T2D rats with SPX. Therefore, these data indicate that the effect of ADSCs ameliorating hyperglycemia and insulin resistance may be partially through promoting spleen-derived anti-inflammatory cytokine IL-10 expression. These novel findings further confirmed the essential role of the spleen in the ADSC treatment of T2D and provide an important theoretical basis for the potential application of ADSCs in T2D therapy.
['Zhang|Jinying|J|', 'Deng|Zihui|Z|', 'Jin|Liyuan|L|', 'Yang|Chen|C|', 'Liu|Jiejie|J|', 'Song|Haijing|H|', 'Han|Weidong|W|', 'Si|Yiling|Y|']
D000273:Adipose Tissue D000818:Animals D000893:Anti-Inflammatory Agents D001786:Blood Glucose D016207:Cytokines D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D059305:Diet, High-Fat D004195:Disease Models, Animal D006943:Hyperglycemia D007249:Inflammation D007333:Insulin Resistance D016753:Interleukin-10 D008297:Male D051381:Rats D017207:Rats, Sprague-Dawley D013154:Spleen D013234:Stem Cells D014409:Tumor Necrosis Factor-alpha
type 2 diabetes spleen hyperglycemia inflammatory insulin sensitivity