Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels

TY - JOUR

T1 - Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels

AU - Plomgaard, Peter

AU - Hansen, Jakob S.

AU - Ingerslev, Bodil

AU - Clemmesen, Jens O.

AU - Secher, Niels H.

AU - van Hall, Gerrit

AU - Fritsche, Andreas

AU - Weigert, Cora

AU - Lehmann, Rainer

AU - Häring, Hans Ulrich

AU - Heni, Martin

PY - 2019

Y1 - 2019

N2 - Aims: To evaluate the effects of brain insulin on endogenous glucose production in fasting humans, with a focus on hepatic glucose release by performing a randomized, placebo-controlled, blinded, crossover experiment. Materials and methods: On two separate days, 2 H 2 -glucose was infused to nine healthy lean men, and blood was sampled from the hepatic vein and a radial artery. On day 1, participants received 160 U human insulin through nasal spray, and on day 2 they received placebo spray, together with an intravenous insulin bolus to mimic spillover of nasal insulin to the circulation. Hepatic glucose fluxes and endogenous glucose production were calculated. Results: Plasma insulin concentrations were similar on the two study days, and no differences in whole-body endogenous glucose production or hepato-splanchnic glucose turnover were detected. Conclusions: Nasal administration of insulin does not influence whole-body or hepatic glucose production in fasting humans. By contrast, pharmacological delivery of insulin to the brain might modulate insulin effectiveness in glucose-producing tissue when circulating insulin levels are elevated; therefore, the metabolic consequences of brain insulin action appear to be dependent on metabolic prandial status.

AB - Aims: To evaluate the effects of brain insulin on endogenous glucose production in fasting humans, with a focus on hepatic glucose release by performing a randomized, placebo-controlled, blinded, crossover experiment. Materials and methods: On two separate days, 2 H 2 -glucose was infused to nine healthy lean men, and blood was sampled from the hepatic vein and a radial artery. On day 1, participants received 160 U human insulin through nasal spray, and on day 2 they received placebo spray, together with an intravenous insulin bolus to mimic spillover of nasal insulin to the circulation. Hepatic glucose fluxes and endogenous glucose production were calculated. Results: Plasma insulin concentrations were similar on the two study days, and no differences in whole-body endogenous glucose production or hepato-splanchnic glucose turnover were detected. Conclusions: Nasal administration of insulin does not influence whole-body or hepatic glucose production in fasting humans. By contrast, pharmacological delivery of insulin to the brain might modulate insulin effectiveness in glucose-producing tissue when circulating insulin levels are elevated; therefore, the metabolic consequences of brain insulin action appear to be dependent on metabolic prandial status.

KW - basal insulin

KW - clinical physiology

KW - liver

U2 - 10.1111/dom.13615

DO - 10.1111/dom.13615

M3 - Journal article

C2 - 30552787

AN - SCOPUS:85060206126

SN - 1462-8902

VL - 21

SP - 993

EP - 1000

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 4

ER -