title: Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men.
abstract: OBJECTIVE
  Glutamatergic pathways are assumed to play a critical role in the hormonal stress response to hypoglycaemia. In rats, glutamate signalling at the amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor contributes to hormone release induced by behavioural stressors. We hypothesised that blocking the AMPA receptor by caroverine in healthy men would impair their perception of neuroglycopenia and thereby diminish hormonal counter-regulation as well as symptoms of hypoglycaemia, as a model of stress.
  
  
  METHODS
  In a balanced double-blind study, two hypoglycaemic clamp sessions (mean blood glucose 2.4 mmol/l for 50 min) were performed in ten healthy men during intravenous administration of 80 mg caroverine or placebo. We assessed concentrations of counter-regulatory hormones as well as subjective symptoms related to hypoglycaemia.
  
  
  RESULTS
  AMPA receptor antagonisation by caroverine did not influence the perception of neuroglycopenic and autonomic hypoglycaemia-associated symptoms (p > 0.39 for all). Notwithstanding, caroverine did increase basal and counter-regulatory glucagon secretion (p < 0.002) and slightly enhanced counter-regulatory growth hormone concentrations (p = 0.07). Counter-regulatory release of ACTH, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine) did not differ between conditions (p > 0.11 for all).
  
  
  CONCLUSIONS
  Antagonising AMPA receptor signalling by caroverine infusion failed to diminish and even slightly amplified counter-regulatory hormone release during hypoglycaemia in healthy men. The discrepancy with previous findings in rats may be due to different dosages or administration routes and calls for further investigations on the role of AMPA receptor signalling in hypoglycaemia counter-regulation in humans.
authors.affiliation: Department of Internal Medicine I, University of Luebeck, Luebeck, Germany. Johanna.Klement@uk-sh.de
authors.forename: J
authors.initials: J
authors.lastname: Klement
authors.forename: I
authors.initials: I
authors.lastname: Pais
authors.forename: M
authors.initials: M
authors.lastname: Hallschmid
authors.forename: C
authors.initials: C
authors.lastname: Hubold
authors.forename: A
authors.initials: A
authors.lastname: Knispel
authors.forename: K M
authors.initials: KM
authors.lastname: Oltmanns
authors.forename: B
authors.initials: B
authors.lastname: Schultes
authors.forename: J
authors.initials: J
authors.lastname: Born
authors.forename: A
authors.initials: A
authors.lastname: Peters