Camilla S Christensen1, Dan P Christensen1, Morten Lundh1, Mattias S Dahllöf1, Tobias N Haase1, Jessica M Velasquez1, Matthew J Laye1, Thomas Mandrup-Poulsen1, Thomas P J Solomon1. 1. 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.
Abstract
CONTEXT: 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. DESIGN: In vitro models were used. SETTING: University. PARTICIPANTS: Healthy subjects. INTERVENTION(S): 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). MAIN OUTCOME MEASURE(S): 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.
CONTEXT: 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. DESIGN: In vitro models were used. SETTING: University. PARTICIPANTS: Healthy subjects. INTERVENTION(S): 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). MAIN OUTCOME MEASURE(S): 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: Raphael P H Meier; Hiroshi Noguchi; Yvonne M Kelly; Minnie Sarwal; Giulia Conti; Casey Ward; Ran Halleluyan; Mehdi Tavakol; Peter G Stock; Chris E Freise Journal: Transplant Direct Date: 2020-09-25