Inappropriate glucagon secretion contributes to hyperglycemia in inflammatory disease. Previous work implicates the pro-inflammatory cytokine, interleukin-6 (IL-6), in glucagon secretion. IL-6 knock-out mice have a blunted glucagon response to lipopolysaccharide (LPS) that is restored by intravenous replacement of IL-6. Given that IL-6 has previously been demonstrated to have a transcriptional (i.e. slow) effect on glucagon secretion from islets, I hypothesized that the rapid increase in glucagon following LPS occurred by a faster mechanism such as by action within the brain. Using chronically catheterized, conscious mice, it was found that central IL-6 stimulates glucagon secretion uniquely in the presence of an accompanying stressor (hypoglycemia or LPS). Contrary to the original hypothesis, however, IL-6 was found to amplify glucagon secretion in two ways: IL-6 not only stimulates glucagon secretion via the brain but also by direct action on islets. Interestingly, IL-6 augments glucagon secretion from both sites only in the presence of an accompanying stressor (such as epinephrine). Given that both adrenergic tone and plasma IL-6 are elevated in multiple inflammatory diseases, the interactions of the IL-6 and catecholaminergic signaling pathways in regulating GCG secretion may contribute to our present understanding of these diseases.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12312014-082201 |
| Date | 07 January 2015 |
| Creators | Barnes, Tammy Michelle |
| Contributors | David H. Wasserman, Ph.D., David A. Jacobson, Ph.D., Danny G. Winder, Ph.D., John M. Stafford, M.D., Ph.D., David Robertson, M.D. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12312014-082201/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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