Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans

SOOP, Mattias, DUXBURY, Helen, AGWUNOBI, Anselm O, GIBSON, J Martin, HOPKINS, Stephen J, CHILDS, Charmaine, COOPER, Robert G, MAYCOCK, Paula, LITTLE, Roderick A and CARLSON, Gordon L (2002). Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans. American journal of physiology. Endocrinology and metabolism, 282 (6), E1276-85.

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Abstract

Type 2 diabetes is associated with biochemical evidence of low-grade inflammation, and experimental studies have suggested that both insulin and glucose affect inflammatory responses. To determine the effect of in vivo changes in glucose availability and plasma insulin concentrations in humans, we administered 20 U/kg Escherichia coli lipopolysaccharide (LPS) or saline (control) to 14 subjects during a euglycemic hyperinsulinemic clamp (n = 6) or an infusion of sterile saline (n = 8). Parallel in vitro studies on human whole blood were undertaken to determine whether there was a direct effect of glucose, insulin, and leptin on proinflammatory cytokine production. Infusion of glucose and insulin significantly amplified and/or prolonged the cardiovascular, plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and counterregulatory hormone responses to LPS, whereas the effects on fever, plasma norepinephrine concentrations, and oxygen consumption were unaffected. In vitro studies showed no modulation of LPS-stimulated IL-6 or TNF-alpha production by glucose, insulin, or leptin at physiologically relevant concentrations. Hyperinsulinemia indirectly enhances key components of the systemic inflammatory and stress responses in this human model of infection.

Item Type:	Article
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Centre for Health and Social Care Research
Identification Number:	https://doi.org/10.1152/ajpendo.00535.2001
Page Range:	E1276-85
Depositing User:	Timothy Wetherill
Date Deposited:	07 Nov 2014 16:17
Last Modified:	18 Mar 2021 19:15
URI:	https://shura.shu.ac.uk/id/eprint/8724

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