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Am J Physiol Endocrinol Metab. 2014 Nov 15;307(10):E896-905. doi: 10.1152/ajpendo.00343.2014. Epub 2014 Sep 9.

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

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
2
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee owen.mcguinness@vanderbilt.edu.

Abstract

Inappropriate 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.

KEYWORDS:

endotoxemia; glucagon; hypoglycemia; inflammation; interleukin-6

PMID:
25205821
PMCID:
PMC4233256
DOI:
10.1152/ajpendo.00343.2014
[Indexed for MEDLINE]
Free PMC Article

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