Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Evidence for glucagon secretion and function within the human gut

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Hypophosphatemic Hypovitaminosis D induces Osteomalacia in the adult female rat

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Activin A determines steroid levels and composition in the fetal testis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Association of In Utero Persistent Organic Pollutant Exposure with Placental Thyroid Hormones

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Roles of RFRP-3 in the Daily and Seasonal Regulation of Reproductive Activity in Female Syrian Hamsters

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Differential effects of bile acids on the postprandial secretion of gut hormones: a randomized crossover study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease

    Publikation: Bidrag til tidsskriftReviewpeer review

  3. Plasma levels of glucagon but not GLP-1 are elevated in response to inflammation in humans

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Emily W Sun
  • Alyce M Martin
  • Dayan de Fontgalland
  • Luigi Sposato
  • Philippa Rabbitt
  • Paul Hollington
  • David A Wattchow
  • Alexander D Colella
  • Tim Chataway
  • Nicolai J Wewer Albrechtsen
  • Nick J Spencer
  • Richard L Young
  • Damien J Keating
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftEndocrinology
Vol/bind162
Udgave nummer4
Sider (fra-til)1-12
Antal sider12
ISSN0013-7227
DOI
StatusUdgivet - 1 apr. 2021

ID: 64231140