title: Early endotoxemia increases peripheral and hepatic insulin sensitivity in healthy humans.
abstract: BACKGROUND
  Sepsis-induced hypoglycemia is a well known, but rare, event of unknown origin.
  
  
  OBJECTIVE
  The aim of the study was to obtain insight into the mechanism of sepsis-induced hypoglycemia, focusing on glucose kinetics and insulin sensitivity measured with stable isotopes by using the model of human endotoxemia.
  
  
  METHODS
  Glucose metabolism was measured during two hyperinsulinemic [insulin levels of 100 pmol/liter (low-dose clamp) and 400 pmol/liter (medium-dose clamp)] euglycemic (5 mmol/liter) clamps on two occasions: without or with lipopolysaccharide (LPS).
  
  
  METHODS
  The study was conducted at the Academic Medical Center, Metabolic and Clinical Research Unit (Amsterdam, The Netherlands).
  
  
  METHODS
  Eighteen healthy male volunteers participated in the study.
  
  
  METHODS
  A hyperinsulinemic euglycemic (5 mmol/liter) clamp with LPS (two groups of six subjects; insulin infusion at rates of either 10 or 40 mU.m(-2).min(-1)) or without LPS (n = 6; both insulin infusions in same subjects).
  
  
  METHODS
  We measured hepatic and peripheral insulin sensitivity.
  
  
  RESULTS
  Hepatic insulin sensitivity, defined as a decrease in endogenous glucose production during hyperinsulinemia (100 pmol/liter), was higher in the LPS group compared to the control group (P = 0.010). Insulin-stimulated peripheral glucose uptake was higher in both clamps after LPS compared to the control setting (P = 0.006 and 0.010), despite a significant increase in the plasma concentrations of norepinephrine and cytokines in the LPS group during both clamps.
  
  
  CONCLUSIONS
  These data indicate that shortly (2 h) after administration of LPS, peripheral and hepatic insulin sensitivity increase. This may contribute to the hypoglycemia occurring in some patients with critical illness, especially in the setting of intensive insulin therapy.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medial Center, Amsterdam, The Netherlands. s.n.vandercrabben@umcutrecht.nl
authors.forename: Saskia N
authors.initials: SN
authors.lastname: van der Crabben
authors.forename: Regje M E
authors.initials: RM
authors.lastname: Blümer
authors.forename: Michiel E
authors.initials: ME
authors.lastname: Stegenga
authors.forename: Mariëtte T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Hans P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D006262:Health; D006728:Hormones / Q000097:blood; D006801:Humans; D007260:Infusion Pumps; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D006728:Hormones; D007328:Insulin; D008070:Lipopolysaccharides