Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans.
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.
Soop
Mattias
M
North West Injury Research Collaboration, Hope Hospital, Salford, M6 8HD, United Kingdom.
Duxbury
Helen
H
Agwunobi
Anselm O
AO
Gibson
J Martin
JM
Hopkins
Stephen J
SJ
Childs
Charmaine
C
Cooper
Robert G
RG
Maycock
Paula
P
Little
Roderick A
RA
Carlson
Gordon L
GL
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001831:Body Temperature; D016207:Cytokines / Q000096:biosynthesis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D004926:Escherichia coli; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D007249:Inflammation / Q000097:blood / Q000150:complications; D007328:Insulin / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D020738:Leptin / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D011674:Pulse; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine