title: Skeletal Muscle to Pancreatic β-Cell Cross-talk: The Effect of Humoral Mediators Liberated by Muscle Contraction and Acute Exercise on β-Cell Apoptosis.
abstract: BACKGROUND
  Mechanisms explaining exercise-induced β-cell health are unknown.
  
  
  OBJECTIVE
  This study aimed to define the role of muscle contraction and acute exercise-derived soluble humoral mediators on β-cell health.
  
  
  METHODS
  In vitro models were used.
  
  
  METHODS
  University.
  
  
  METHODS
  Healthy subjects.
  
  
  METHODS
  Conditioned media (CM) were collected from human skeletal muscle (HSkM) cells treated with or without electrical pulse stimulation (EPS). Antecubital and femoral venous blood serum were collected before and after an exercise bout. CM and sera with or without IL-6 neutralization were used to incubate insulin-producing INS-1 cells and rat islets for 24 h in the presence or absence of proinflammatory cytokines (IL-1β+IFN-γ).
  
  
  METHODS
  INS-1 and islet apoptosis and accumulated insulin secretion.
  
  
  RESULTS
  IL-1β+IFN-γ increased INS-1 and islet apoptosis and decreased insulin secretion. EPS-treated HSkM cell CM did not affect these variables. Exercise-conditioned antecubital but not femoral sera prevented IL-1β+IFN-γ-induced INS-1 and islet apoptosis. Femoral sera reduced insulin secretion under normal and proinflammatory conditions in INS-1 but not islet cells. EPS increased HSkM cell IL-6 secretion and exercise increased circulating IL-6 levels in antecubital and femoral serum. IL-6 neutralization demonstrated that muscle-derived IL-6 prevents INS-1 and islet apoptosis in the absence of IL-1β+IFN-γ, but augments apoptosis under proinflammatory conditions, and that muscle-derived IL-6 supports islet insulin secretion in the absence of IL-1β+IFN-γ.
  
  
  CONCLUSIONS
  Unidentified circulating humoral mediators released during exercise prevent proinflammatory cytokine-induced β-cell apoptosis. Muscle-derived mediators released during exercise suppress β-cell insulin secretion. Furthermore, muscle-derived IL-6 seems to prevent β-cell apoptosis under normal conditions but contributes to β-cell apoptosis under proinflammatory conditions.
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Christensen
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Dan P
authors.initials: DP
authors.lastname: Christensen
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Morten
authors.initials: M
authors.lastname: Lundh
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Mattias S
authors.initials: MS
authors.lastname: Dahllöf
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Haase
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Velasquez
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Laye
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.affiliation: Department of Biomedical Sciences (C.S.C., D.P.C., M.S.D., T.N.H., J.M.V., T.M.-P.), Panum Institute, University of Copenhagen, 2200, Denmark; Centre for Inflammation and Metabolism (J.M.V., M.J.L.), Rigshospitalet, Copenhagen, 2100, Denmark; Department of Molecular Medicine and Surgery (J.M.-P.), Karolinska Institutet, Stockholm, SE-171 77, Sweden; and School of Sport, Exercise, and Rehabilitation Sciences (T.P.J.S.), Centre for Endocrinology, Diabetes, and Metabolism, University of Birmingham, B15 2TT, United Kingdom.
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004558:Electric Stimulation; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055815:Young Adult
chemical_list: D007328:Insulin; D053583:Interleukin-1beta; D007371:Interferon-gamma