Open AccessMacrophage migration inhibitory factor deficiency augments cardiac dysfunction in Type 1 diabetic murine cardiomyocytes
Author(s) -
TONG Chao,
MORRISON Alex,
YAN Xiaoyan,
ZHAO Peng,
YEUNG Eddie D.,
WANG Jingying,
XIE Jianxin,
LI Ji
Publication year - 2010
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/j.1753-0407.2010.00088.x
Subject(s) - macrophage migration inhibitory factor , medicine , inhibitory postsynaptic potential , diabetes mellitus , endocrinology , cardiac dysfunction , type 1 diabetes , macrophage , type 2 diabetes , immunology , heart failure , cytokine , in vitro , biology , biochemistry
Background: It has become evident that macrophage migration inhibitory factor (MIF) is associated with the development of Type 1 diabetes mellitus. The aim of the present study was to determine whether MIF plays a role in cardiac contractile dysfunction in T1DM mice. Methods: Mechanical and intracellular Ca 2+ properties were measured in cardiomyocytes isolated from wild‐type (WT) and MIF‐knockout (MIF‐KO) mice administrated or not streptozotocin (200 mg/kg, i.p.). Relative stress signaling was evaluated using western blot analysis. Results: Peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/dt) were reduced and the duration of relengthening (TR90) was prolonged in both WT and MIF‐KO cardiomyocytes treated with STZ ( P < 0.01 vs control), which may be associated with reduced intracellular Ca 2+ decay in both groups. However, STZ‐treated WT cardiomyocytes demonstrated significantly better contractile function and intracellular Ca 2+ properties compared with STZ‐treated MIF‐KO cardiomyocytes (all P < 0.05). Interestingly, the physiological data clearly showed that blood glucose levels were significantly higher in STZ‐treated MIF‐KO mice than STZ‐treated WT mice ( P < 0.01). Moreover, phosphorylation of AMP‐activated protein kinase (AMPK) and its direct downstream target acetyl‐CoA carboxylase (ACC) was markedly lower in hearts from STZ‐treated MIF‐KO mice than STZ‐treated WT mice ( P < 0.05). There were no significant differences between untreated WT and MIF‐KO control groups. Conclusions: There is a beneficial action of MIF in the management of cardiac dysfunction in T1DM. The cardioprotective effect of MIF may be associated with AMPK signaling.