Interleukin-6 amplifies glucagon secretion: Coordinated control via the brain and pancreas

Tammy M. Barnes, Yolanda F. Otero, Amicia D. Elliott, Alicia D. Locke, Carlo M. Malabanan, Anastasia G. Coldren, Marcela Brissova, David W. Piston, Owen P. McGuinness

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24 Scopus citations


In xappropriate glucagon secretion contributes to hyperglycemia in inflammatory disease. Previous work implicates the proinflammatory cytokine interleukin-6 (IL-6) in glucagon secretion. IL-6-KO 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, we 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, we have demonstrated that central IL-6 stimulates glucagon secretion uniquely in the presence of an accompanying stressor (hypoglycemia or LPS). Contrary to our hypothesis, however, we found that IL-6 amplifies 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.

Original languageEnglish
Pages (from-to)E896-E905
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number10
StatePublished - Nov 15 2014


  • Endotoxemia
  • Glucagon
  • Hypoglycemia
  • Inflammation
  • Interleukin-6


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