Evaluation of the specific effects of intranasal glucagon on circulating glucose and lipid concentrations in healthy males during a pancreatic clamp

5 years ago

Evaluation of the specific effects of intranasal glucagon on circulating glucose and lipid concentrations in healthy males during a pancreatic clamp

Adria Giacca, Priska Stahel, Changting Xiao, Satya Dash, Gary F. Lewis, Khajag Koulajian

Context Intravenous/intramuscular glucagon stimulates hepatic glucose production and adipose lipolysis. Intranasal glucagon (ING) has recently been shown to be an effective treatment for hypoglycaemia. Intranasal administration of hormones increases its central nervous system (CNS) concentration with metabolic effects independent of its plasma concentration, potentially via CNS action. Whether ING has metabolic effects independent of plasma glucagon is unknown. Objective To investigate the specific effects of intranasal glucagon (ING) on plasma glucose, endogenous glucose production (EGP) and lipid concentration. Design Single blind, randomized, crossover study. Setting Academic investigation unit. Intervention 1mg ING or intranasal placebo (INP) administered to 10 healthy men, under conditions of a pancreatic clamp with tracer infusion. As pilot studies showed ING transiently increased plasma glucagon, we infused intravenous glucagon for 30 minutes along with INP to ensure similar plasma glucagon concentrations between interventions. Main outcome measure Plasma glucose, EGP, free fatty acid (FFA) and triglyceride (TG) concentrations Results In the presence of similar plasma glucagon concentrations, the increase in plasma glucose under these experimental conditions was attenuated with ING (mean plasma glucose by ANOVA < 0.001) with reduction in EGP (p = 0.027). No significant differences were seen in plasma FFA and triglyceride. Conclusion ING raises plasma glucose but this route of administration attenuates the gluco-stimulatory effect of glucagon by reducing EGP. This observation invites speculation about a potential CNS effect of glucagon, which requires further investigation. If ING is developed as a treatment for hypoglycaemia, this attenuated effect on plasma glucose should be taken into account. Clinical trials Registration number (clinicaltrials.gov): NCT02740829

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13069