Visual Abstract
Glucagon secretion and signaling are affected in several metabolic disorders including different types of diabetes. To understand these mechanisms better, we investigated the effect of exogeneous glucagon in participants deprived of endogenous glucagon and/or insulin. We included nine middle-aged, normal-weight patients who had undergone total pancreatectomy (PX), eight patients with type 1 diabetes (T1D) and nine healthy controls in a randomized, double-blinded crossover study (groups were matched by age, gender and BMI). Participants received a 2.5-hour intravenous infusion of glucagon (4 ng/kg/min) and placebo (saline), respectively, under fasting conditions with usual basal insulin administration. Glucagon infusion increased plasma glucagon to similar supraphysiologic levels in all groups and increased glucose levels as assessed by baseline-subtracted area under the curve (bsAUC) by 2.2 and 3.5-fold, respectively, in the PX group compared to the T1D group (P=0.015) and control group (P<0.001). Glucagon reduced bsAUC for total amino acids by 2.8 and 2.3-fold, respectively, in the PX group compared to the T1D group (P=0.03) and control group (P=0.08).
In conclusion, well-known actions of glucagon are more pronounced in PX patients compared to matched T1D patients and healthy controls indicating an increased sensitivity to glucagon in response to the underlying loss of pancreatic glucagon secretion in PX patients.
I. Rix: Employee; Self; Zealand Pharma A/S. A. Lund: Speaker's Bureau; Self; Novo Nordisk, Sanofi. L. F. Garvey: None. K. Owen: Employee; Self; Zealand Pharma A/S. C. Hansen: None. G. Van hall: n/a. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.
Innovation Fund Denmark; Novo Nordisk Foundation; A.P. Møller Foundation; Aase and Ejnar Danielsen Foundation; Inge & Per Refhall's Research Grant; Augustinus Foundation
