Glucagon 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, cross-over study design, we therefore measured EE and rates of glucose appearance (glucose RA) during three separate infusion protocols in healthy lean males: A) 10-hour overnight glucagon (GCG) infusion (6 ng/[kg x min]), followed by 3-hour infusion of GCG, octreotide (OCT) and insulin (INS) for basal replacement, B) overnight saline (SAL) infusion, followed by GCG/OCT/INS infusion, C) overnight SAL infusion, followed by SAL/OCT/INS infusion. Sleep EE, measured at 6-7 hours of the overnight infusion, was increased 65-70 kcal/24 hours in A compared to B and C. During the 3-hour infusion, mean resting EE remained significantly increased in A versus C by approximately 50 kcal/24 hours; 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 glucagon dose was of marginal clinical significance.
- Received June 16, 2016.
- Accepted September 28, 2016.
- © 2016 by the American Diabetes Association.