MIF and insulin: Lifetime companions from common genesis to common pathogenesis
2020
Document Type:
Article (Published version)
,
© 2019 Elsevier Ltd
Metadata
Show full item recordAbstract:
Pro-inflammatory nature of macrophage migration inhibitory factor (MIF) has been generally related to the
propagation of inflammatory and autoimmune diseases. But this molecule possesses many other peculiar
functions, unrelated to the immune system, among which is its supportive role in the post-translational modifications of insulin. In this way MIF enables proper insulin conformation within the pancreatic beta cell and its full activity. The inherent or acquired changes in MIF expression might therefore lead to different insulin processing and initiation of autoimmunity. The relation between MIF and insulin does not stop at this point; these two molecules continue to interact during pathological states characterized by inflammation and insulin resistance. In this context, MIF indirectly and negatively influences insulin action by boosting inflammatory environment and disabling target cells to respond to insulin. On the other side, insulin might interfere with MIF action as well, acting as an anti-inflammatory mediator. Therefore, the proper interaction between MIF and insulin is crucial for maintaining homeostasis, while anti-inflammatory therapies based on the systemic MIF blockage may disturb this balance. This review covers MIF-insulin relationship in the physiological and pathological conditions and discusses the approaches for MIF inhibition and their net effect specifically considering possible impact on insulin misfolding and the possible misinterpretation of previous results due to the discovery of MIF functional homolog D-dopachrome tautomerase.
Keywords:
IInsulin; MIF; D-DT; Cytokine; Hormone; Insulin-resistance; Inflammation; DiabetesSource:
Cytokine, 2020, 125, 154792-Funding / projects:
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
- Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis (RS-MESTD-Basic Research (BR or ON)-173035)
DOI: 10.1016/j.cyto.2019.154792
PubMed: 31400637