dc.creator | Barnes, Tammy Michelle | |
dc.date.accessioned | 2020-08-23T16:25:32Z | |
dc.date.available | 2015-01-07 | |
dc.date.issued | 2015-01-07 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-12312014-082201 | |
dc.identifier.uri | http://hdl.handle.net/1803/15355 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | lipopolysaccharide | |
dc.subject | Interleukin-6 | |
dc.subject | glucagon secretion | |
dc.subject | glucagon | |
dc.subject | autonomic | |
dc.subject | hypoglycemia | |
dc.title | Interleukin-6 Enhances Glucagon Secretion: Amplification via the Pancreas and Brain | |
dc.type | dissertation | |
dc.contributor.committeeMember | David A. Jacobson, Ph.D. | |
dc.contributor.committeeMember | Danny G. Winder, Ph.D. | |
dc.contributor.committeeMember | John M. Stafford, M.D., Ph.D. | |
dc.contributor.committeeMember | David Robertson, M.D. | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Molecular Physiology and Biophysics | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-01-07 | |
local.embargo.lift | 2015-01-07 | |
dc.contributor.committeeChair | David H. Wasserman, Ph.D. | |