AMPA receptor antagonist caroverine has no effect on hypoglycaemic counterregulation

Abstract

Introduction: Animal studies have indicated a critical role of glutamate signaling at NMDA and non-NMDA receptors in the regulation of neuroendocrine secretion. The role of the AMPA receptor during insulin induced hypoglycaemia has not been assessed in humans so far. Here we studied the effect of the AMPA receptor antagonist caroverine on hormonal counterregulation during hypoglycaemia. Methods: Two hypoglycaemic clamp experiments (mean blood glucose level 2.4 mmol/l) were performed in 10 subjects after intravenous administration of 80mg caroverine. Counterregulatory hormones (adrenaline, ACTH, cortisol) were measured during baseline and hypoglycaemic plateau. Furthermore, symptoms related to glycaemic changes and aspects of cognitive functions (short-term memory and attention) were assessed. Results: Antagonizing the AMPA receptor with caroverine did not have a significant effect on hormonal counterregulation during hypoglycaemia. Also, cognitive functions and symptoms related to glycaemic changes did not differ between conditions. Conclusion: Results do not provide evidence for a role of caroverine in the release of counterregulatory hormones during hypoglycaemia. Symptoms related to glycaemic changes and aspects of cognitive function were neither sensitive to the systemic administration of 80mg caroverine. Further studies are needed to explore if higher doses of caroverine or other AMPA receptor antagonists have a detectable influence on hormonal counterregulation during hypoglycaemia.