Skeletal Muscle to Pancreatic β-Cell Cross-talk: The Effect of Humoral Mediators Liberated by Muscle Contraction and Acute Exercise on β-Cell Apoptosis
Skeletal Muscle to Pancreatic β-Cell Cross-talk: The Effect of Humoral Mediators Liberated by Muscle Contraction and Acute Exercise on β-Cell Apoptosis
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DOI：
10.1210/jc.2014-4506
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发表时间：
2015-10-01
影响因子：
5.8
通讯作者：
Solomon, Thomas P. J.
中科院分区：
文献类型：
--
作者：
Christensen, Camilla S.;Christensen, Dan P.;Solomon, Thomas P. J.
内容：解释运动诱导的β细胞健康的机制是unknown.Objective：This study aims to define the role of muscle contraction and acute exercise derived soluble humoral mediators on the β-cell healthy.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）.分别于运动前后采集肘前静脉和股静脉血清。CM和有或没有IL-6中和的血清用于在存在或不存在促炎细胞因子（IL-1 β + IFN-γ）的情况下孵育产生胰岛素的INS-1细胞和大鼠胰岛24 h。主要结果测量：INS-1和胰岛细胞凋亡和累积的胰岛素分泌。EPS处理的HSkM细胞CM不影响这些变量。肘前血清而非股血清可预防IL-1 β + IFN-γ诱导的INS-1和胰岛细胞凋亡。在INS-1中，股血清在正常和促炎条件下减少胰岛素分泌，但不减少胰岛细胞。EPS增加HSkM细胞IL-6分泌，运动增加肘前和股血清中循环IL-6水平。IL-6中和表明，肌肉来源的IL-6防止INS-1和胰岛细胞凋亡的IL-1 β + IFN-γ的情况下，但增加促炎条件下的细胞凋亡，和肌肉来源的IL-6支持胰岛胰岛素分泌的IL-1 β + IFN-γ的情况下。结论：不明循环体液介质在运动过程中释放防止促炎性β细胞凋亡。在运动过程中释放的肌肉源性介质抑制β细胞胰岛素分泌。此外，肌肉来源的IL-6似乎在正常条件下防止β细胞凋亡，但在促炎条件下促进β细胞凋亡。
Context: Mechanisms explaining exercise-induced beta-cell health are unknown.Objective: This study aimed to define the role of muscle contraction and acute exercise-derived soluble humoral mediators on beta-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-1 beta + IFN-gamma).Main Outcome Measure(s): INS-1 and islet apoptosis and accumulated insulin secretion.Results: IL-1 beta + IFN-gamma 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-1 beta + IFN-gamma-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-1 beta + IFN-gamma, but augments apoptosis under proinflammatory conditions, and that muscle-derived IL-6 supports islet insulin secretion in the absence of IL-1 beta + IFN-gamma.Conclusions: Unidentified circulating humoral mediators released during exercise prevent proinflammatory cytokine-induced beta-cell apoptosis. Muscle-derived mediators released during exercise suppress beta-cell insulin secretion. Furthermore, muscle-derived IL-6 seems to prevent beta-cell apoptosis under normal conditions but contributes to beta-cell apoptosis under proinflammatory conditions.