62-OR: Evidence of Gut-Derived Glucagon in Man

We have previously shown that totally pancreatectomized patients (PX) and patients with type 2 diabetes (T2D) exhibit hypersecretion of glucagon in response to oral glucose stimulation whereas intravenous glucose suppresses plasma concentrations of glucagon. Here, we evaluated the expression of the gene encoding glucagon (GCG), glucagon peptide content and density of glucagon-positive cells in mucosal biopsies from the upper gastrointestinal tract of PX patients, patients with T2D and nondiabetic controls. Eight PX patients, eight patients with T2D and eight sex, age and BMI-matched healthy controls underwent upper enteroscopy with intestinal biopsy sampling followed by an intraluminal infusion of 100 ml 50% (w/v) glucose solution with frequent blood sampling. The mucosal biopsies were subjected to mRNA sequencing, immunohistochemistry using a new glucagon-directed C-terminal monoclonal antibody, peptide extraction and subsequent measurements of tissue concentrations of glucagon and other proglucagon-derived peptides. GCG expression in the small intestine was 3 to 4-fold higher in PX and T2D patients compared to controls (P Disclosure M. Baekdal: None. A.B. Lund: None. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S. Speaker9s Bureau; Self; Merck Sharp & Dohme Corp. J.I. Egholk: None. T. Jorsal: None. C.T. Juel: None. K.D. Galsgaard: None. J. Hunt: None. J.F. Rehfeld: None. K. Rigbolt: Employee; Self; Gubra. Stock/Shareholder; Self; Gubra. S.U. Friis: Stock/Shareholder; Self; Alk-Abello B, Bavarian Nordic, H. Lundbeck A/S, Lundbeck, Novo Nordisk A/S. C. Orskov: None. S.S. Poulsen: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsboll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker9s Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S. Funding European Foundation for the Study of Diabetes; Novo Nordisk Foundation; Aase og Ejnar Danielsens Foundation; A.P. Moller Foundation