Macrophage migration inhibitory factor deficiency augments cardiac dysfunction in Type 1 diabetic murine cardiomyocytes

Abstract

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. 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. 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. 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.