Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital

Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Bilio-enteric flow and plasma concentrations of bile acids after gastric bypass and sleeve gastrectomy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Plasma GDF15 levels are similar between subjects after bariatric surgery and matched controls and are unaffected by meals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Neprilysin inhibition increases glucagon levels in humans and mice with potential effects on amino acid metabolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Factors associated with favorable changes in food preferences after bariatric surgery

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Ida M Modvig
  • Daniel B Andersen
  • Kaare V Grunddal
  • Rune E Kuhre
  • Christoffer Martinussen
  • Charlotte B Christiansen
  • Cathrine Ørskov
  • Pierre Larraufie
  • Richard G Kay
  • Frank Reimann
  • Fiona M Gribble
  • Bolette Hartmann
  • Kirstine N Bojsen-Møller
  • Sten Madsbad
  • Nicolai J Wewer Albrechtsen
  • Jens J Holst
Vis graf over relationer

OBJECTIVES: Gastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release.

METHODS: A specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation.

RESULTS: Plasma postprandial secretin was more than doubled in humans after RYGB (P < 0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased the secretion of secretin in a sodium-glucose cotransporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P < 0.05) from the perfused rat pancreas but affected neither insulin (P = 0.2) nor glucagon (P = 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P = 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P = 0.004).

CONCLUSIONS: Glucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies.

TidsskriftInternational Journal of Obesity
Udgave nummer9
Sider (fra-til)1859-1871
Antal sider13
StatusUdgivet - 1 sep. 2020

ID: 59245829