258-OR: The Glucagonotropic Effect of GLP-2 during Hypoglycemia, Euglycemia, and Hyperglycemia in Healthy Men: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Abstract

To determine whether the glucagonotropic gut-derived hormone glucagon-like peptide 2 (GLP-2) might be exploited as a safeguard against insulin-induced hypoglycemia, we evaluated the effects of exogenous GLP-2 during hypoglycemia, euglycemia and hyperglycemia. Ten healthy, young men underwent six randomized study days: two insulin-induced hypoglycemic clamps (2.5 mmol/L), two euglycemic clamps, and two hyperglycemic clamps (10 mmol/L). At each glycemic level, double-blinded intravenous infusion with GLP-2 (6 pmol/kg/minfrom −10 to 0 min, and 2 pmol/kg/min from 0 to 90 min) or placebo was given. Compared to placebo, exogenous GLP-2 increased glucagon secretion (assessed by baseline-subtracted area under curve) during euglycemia ([mean ± SD] −141±159 pmol/L×min vs. 261±200 pmol/L×min, P=0.0005), but not during hypo- and hyperglycemia. However, compared to placebo, GLP-2 increased glucagon secretion during the initial 40 minutes of the hypoglycemic clamp (38±81 pmol/L×min vs. 174±82 pmol/L×min, P=0.0007).In conclusion, the glucagonotropic effect of GLP-2 is evident at euglycemia and - to a lesser extent - during hypoglycemia, but not during hyperglycemia; positioning GLP-2 as a potential plasma glucose-stabilizer, which perhaps may be utilized therapeutically as a safeguard against insulin-induced hypoglycemia.View largeDownload slideView largeDownload slide DisclosureN. L. Hansen: None. T. Magnussen: None. 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. B. Hartmann: None. M. B. Christensen: None. A. Lund: Speaker’s Bureau; Self; Novo Nordisk, Sanofi. 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.