title: Effects of 13-Hour Hyperglucagonemia on Energy Expenditure and Hepatic Glucose Production in Humans.
abstract: Glucagon (GCG) acutely stimulates energy expenditure (EE) and hepatic glucose production (HGP) in humans, but whether these effects persist during hyperglucagonemia of longer duration is unclear. Using a prospective, randomized, single-blind, crossover study design, we therefore measured EE and rates of glucose appearance (glucose RA) during three separate infusion protocols in healthy lean males: A) 10-h overnight GCG infusion (6 ng/[kg × min]) followed by 3-h infusion of GCG, octreotide (OCT), and insulin (INS) for basal replacement; B) overnight saline (SAL) infusion followed by GCG/OCT/INS infusion; and C) overnight SAL infusion followed by SAL/OCT/INS infusion. Sleep EE, measured at 6 to 7 h of the overnight infusion, was increased 65-70 kcal/24 h in A compared with B and C. During the 3-h infusion, mean resting EE remained significantly increased in A versus C by ∼50 kcal/24 h; in B, resting EE increased with a statistical trend but was not significantly greater than in C. Glucose RA increased to comparable levels in A and B. We conclude that in healthy lean males, stimulation of EE and HGP is sustained during hyperglucagonemia of longer duration when insulin secretion is inhibited. The increase in EE at the present GCG dose was of marginal clinical significance.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Manu
authors.initials: M
authors.lastname: Chakravarthy
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Parsons
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Lassman
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Kristin
authors.initials: K
authors.lastname: Butterfield
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Anita Y H
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Stephen
authors.initials: S
authors.lastname: Previs
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Spond
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Shan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bock
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
authors.forename: Fanchao
authors.initials: F
authors.lastname: Yi
authors.affiliation: MEI Research, Ltd., Edina, MN.
authors.forename: Jon
authors.initials: J
authors.lastname: Moon
authors.affiliation: MEI Research, Ltd., Edina, MN.
authors.forename: Erica
authors.initials: E
authors.lastname: Wohlers-Kariesch
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL christian.meyer@flhosp.org.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects*; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose