1. Academic Validation
  2. Evidence for Glucagon Secretion and Function Within the Human Gut

Evidence for Glucagon Secretion and Function Within the Human Gut

  • Endocrinology. 2021 Apr 1;162(4):bqab022. doi: 10.1210/endocr/bqab022.
Emily W Sun 1 Alyce M Martin 1 Dayan de Fontgalland 2 Luigi Sposato 2 Philippa Rabbitt 2 Paul Hollington 2 David A Wattchow 2 Alexander D Colella 1 Tim Chataway 1 Nicolai J Wewer Albrechtsen 3 Nick J Spencer 1 Richard L Young 4 5 Damien J Keating 1
Affiliations

Affiliations

  • 1 Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
  • 2 Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia.
  • 3 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • 4 Adelaide Medical School and NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia.
  • 5 Nutrition, Diabetes and Metabolism, Lifelong Health, South Australia Health and Medical Research Institute, Adelaide, SA, Australia.
Abstract

Glucagon is secreted by pancreatic α cells in response to hypoglycemia and increases hepatic glucose output through hepatic glucagon receptors (GCGRs). There is evidence supporting the notion of extrapancreatic glucagon but its source and physiological functions remain elusive. Intestinal tissue samples were obtained from patients undergoing surgical resection of Cancer. Mass spectrometry analysis was used to detect glucagon from mucosal lysate. Static incubations of mucosal tissue were performed to assess glucagon secretory response. Glucagon concentration was quantitated using a highly specific sandwich enzyme-linked immunosorbent assay. A Cholesterol uptake assay and an isolated murine colonic motility assay were used to assess the physiological functions of intestinal GCGRs. Fully processed glucagon was detected by mass spectrometry in human intestinal mucosal lysate. High glucose evoked significant glucagon secretion from human ileal tissue independent of sodium glucose cotransporter and KATP channels, contrasting glucose-induced glucagon-like peptide 1 (GLP-1) secretion. The GLP-1 Receptor agonist Exendin-4 attenuated glucose-induced glucagon secretion from the human ileum. GCGR blockade significantly increased Cholesterol uptake in human ileal crypt culture and markedly slowed ex vivo colonic motility. Our findings describe the human gut as a potential source of extrapancreatic glucagon and demonstrate a novel enteric glucagon/GCGR circuit with important physiological functions beyond glycemic regulation.

Keywords

GLP-1; enteroendocrine cells; glucagon; gut hormones.

Figures
Products