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

Soop, M, Duxbury, H, Agwunobi, A, Gibson, JM, Hopkins, SJ, Childs, C, Cooper, RG, Maycock, PF, Little, RA, Carlson, GL

Am J Physiol Endocrinol Metab. 2002;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.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Publication form:
Published date:
Place of publication:
United States
Volume:
282( 6)
Start page:
E1276
End page:
85
Pagination:
E1276-85
Access state:
Active

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:1d14221
Created:
30th August, 2009, 13:06:26
Last modified:
5th March, 2013, 19:24:58