title: Exercise increases pancreatic β-cell viability in a model of type 1 diabetes through IL-6 signaling.
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 carboxamide1-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.
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Flavia M M
authors.initials: FM
authors.lastname: Paula
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Nayara C
authors.initials: NC
authors.lastname: Leite
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Emerielle C
authors.initials: EC
authors.lastname: Vanzela
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Mirian A
authors.initials: MA
authors.lastname: Kurauti
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Freitas-Dias
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: *Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil; and Department of Physical Therapy, Laboratory of Exercise Physiology and Genetics, University of Pernambuco, Petrolina, Brazil czoppi@unicamp.br.
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Zoppi
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D005947:Glucose
keywords: apoptosis; cytokine signaling myokines; pancreatic islets