Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic cells. Exercise training enhances beta cell mass in T1D. Here, we investigated how exercise signals beta cells in T1D condition. For this, we used several approaches. Wild-type and IL-6 knockout (KO) C57BL/6 mice were exercised. Afterward, islets from control and trained mice were exposed to inflammatory cytokines (IL-1 beta plus IFN-gamma). Islets from control mice and beta-cell lines (INS-1E and MIN6) were incubated with serum from control or trained mice or medium obtained from 5-aminoimidazole-4 carboxamide1-beta-D-ribofuranoside (AICAR)-treated C2C12 skeletal muscle cells. Subsequently, islets and beta cells were exposed to IL-1 beta plus IFN-gamma. Proteins were assessed by immunoblotting, apoptosis was determined by DNA-binding dye propidium iodide fluorescence, and NO center dot was estimated by nitrite. Exercise reduced 25, 75, and 50 of the IL-1 beta plus IFN-gamma-induced iNOS, nitrite, and cleaved caspase-3 content, respectively, in pancreatic islets. Serum from trained mice and medium from AICAR-treated C2C12 cells reduced beta-cell death, induced by IL-1 beta plus IFN-gamma treatment, in 15 and 38, respectively. This effect was lost in samples treated with IL-6 inhibitor or with serum from exercised IL-6 KO mice. In conclusion, muscle contraction signals beta-cell survival in T1D through IL-6.
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