Exercise increases pancreatic β‐cell viability in a model of type 1 diabetes through IL‐6 signaling

• Published in: The FASEB journal 2015-05, Vol.29 (5), p.1805-1816
• Main Authors: Paula, Flavia M. M., Leite, Nayara C., Vanzela, Emerielle C., Kurauti, Mirian A., Freitas‐Dias, Ricardo, Carneiro, Everardo M., Boschero, Antonio C., Zoppi, Claudio C.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Blotting, Western; Cell Proliferation; Cells, Cultured; cytokine signaling myokines; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - therapy; Glucose - metabolism; Insulin - metabolism; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Interferon-gamma - pharmacology; Interleukin-1beta - pharmacology; Interleukin-6 - physiology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Nitric Oxide - metabolism; pancreatic islets; Physical Conditioning, Animal; Radioimmunoassay; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.14-264820

ABSTRACT Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic β cells. Exercise training enhances β‐cell mass in T1D. Here, we investigated how exercise signals β 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‐1β plus IFN‐γ). Islets from control mice and β‐cell lines (INS‐1E and MIN6) were incubated with serum from control or trained mice or medium obtained from 5‐aminoimidazole‐4 carboxamide 1‐β‐d‐ribofuranoside (AICAR)‐treated C2C12 skeletal muscle cells. Subsequently, islets and β cells were exposed to IL‐1β plus IFN‐γ. Proteins were assessed by immunoblotting, apoptosis was determined by DNA‐binding dye propidium iodide fluorescence, and NO* was estimated by nitrite. Exercise reduced 25, 75, and 50% of the IL‐1β plus IFN‐γ‐induced iNOS, nitrite, and cleaved caspase‐3 content, respectively, in pancreatic islets. Serum from trained mice and medium from AICAR‐treated C2C12 cells reduced β‐cell death, induced by IL‐1β plus IFN‐γ 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 β‐cell survival in T1D through IL‐6.—Paula, F.M.M., Leite, N. C., Vanzela, E. C., Kurauti, M. A., Freitas‐Dias, R., Carneiro, E. M., Boschero, A. C., Zoppi, C. C. Exercise increases pancreatic β‐cell viability in a model of type 1 diabetes through IL‐6 signaling. FASEB J. 29, 1805‐1816 (2015). www.fasebj.org