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Title page for ETD etd-12312014-082201

Type of Document Dissertation
Author Barnes, Tammy Michelle
Author's Email Address tammy.m.lundblad@vanderbilt.edu
URN etd-12312014-082201
Title Interleukin-6 Enhances Glucagon Secretion: Amplification via the Pancreas and Brain
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
David H. Wasserman, Ph.D. Committee Chair
Danny G. Winder, Ph.D. Committee Member
David A. Jacobson, Ph.D. Committee Member
David Robertson, M.D. Committee Member
John M. Stafford, M.D., Ph.D. Committee Member
  • lipopolysaccharide
  • Interleukin-6
  • glucagon secretion
  • glucagon
  • autonomic
  • hypoglycemia
Date of Defense 2014-12-08
Availability unrestricted
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.
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