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

Barnes TM, Otero YF, Elliott AD, Locke AD, Malabanan CM, Coldren AG, Brissova M, Piston DW, McGuinness OP
Am J Physiol Endocrinol Metab. 2014 307 (10): E896-905

PMID: 25205821 · PMCID: PMC4233256 · DOI:10.1152/ajpendo.00343.2014

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.

Copyright © 2014 the American Physiological Society.

MeSH Terms (15)

Animals Brain Epinephrine Glucagon Glucagon-Secreting Cells Glucose Clamp Technique Hypoglycemia Interleukin-6 Islets of Langerhans Lipopolysaccharides Mice Mice, Inbred C57BL Mice, Knockout Stress, Physiological Sympathomimetics

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