Benigni, Fabio and Atsumi, Toshiya and Calandra, Thierry and Metz, Christine and Echtenacher, Bernd and Peng, Tina and Bucala, Richard (2000) The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. JOURNAL OF CLINICAL INVESTIGATION, 106 (10). pp. 1291-1300. ISSN 0021-9738
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; FACTOR MIF; TNF-ALPHA; SKELETAL-MUSCLE; REGULATORY ROLE; FRUCTOSE 2,6-BISPHOSPHATE; LACTATE PRODUCTION; FAT-CELLS; IN-VIVO; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Mar 2022 07:03 |
| Last Modified: | 21 Mar 2022 07:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42099 |
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