The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle

Details

Serval ID
serval:BIB_06455A55651E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle
Journal
Journal of Clinical Investigation
Author(s)
Benigni  F., Atsumi  T., Calandra  T., Metz  C., Echtenacher  B., Peng  T., Bucala  R.
ISSN
0021-9738 (Print)
Publication state
Published
Issued date
11/2000
Volume
106
Number
10
Pages
1291-300
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Abstract
Severe infection or tissue invasion can provoke a catabolic response, leading to severe metabolic derangement, cachexia, and even death. Macrophage migration inhibitory factor (MIF) is an important regulator of the host response to infection. Released by various immune cells and by the anterior pituitary gland, MIF plays a critical role in the systemic inflammatory response by counterregulating the inhibitory effect of glucocorticoids on immune-cell activation and proinflammatory cytokine production. We describe herein an unexpected role for MIF in the regulation of glycolysis. The addition of MIF to differentiated L6 rat myotubes increased synthesis of fructose 2,6-bisphosphate (F2,6BP), a positive allosteric regulator of glycolysis. Increased expression of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) enhanced F2,6BP production and, consequently, cellular lactate production. The catabolic effect of TNF-alpha on myotubes was mediated by MIF, which served as an autocrine stimulus for F2, 6BP production. TNF-alpha administered to mice decreased serum glucose levels and increased muscle F2,6BP levels; pretreatment with a neutralizing anti-MIF mAb completely inhibited these effects. Anti-MIF also prevented hypoglycemia and increased muscle F2,6BP levels in TNF-alpha-knockout mice that were administered LPS, supporting the intrinsic contribution of MIF to these inflammation-induced metabolic changes. Taken together with the recent finding that MIF is a positive, autocrine stimulator of insulin release, these data suggest an important role for MIF in the control of host glucose disposal and carbohydrate metabolism.
Keywords
Animals Cell Line Cell Movement/physiology Fructosediphosphates/*biosynthesis Glucose/*metabolism Glycolysis/drug effects Humans Lactic Acid/*biosynthesis Liver/metabolism Macrophage Migration-Inhibitory Factors/*metabolism/pharmacology Macrophages/metabolism Mice Muscles/metabolism Phosphofructokinase-2 Phosphoric Monoester Hydrolases/metabolism Phosphotransferases (Alcohol Group Acceptor)/metabolism Rats Tumor Cells, Cultured Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 13:28
Last modification date
20/08/2019 12:28
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