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

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Modvig, Ida M ; Andersen, Daniel B ; Grunddal, Kaare V ; Kuhre, Rune E ; Martinussen, Christoffer ; Christiansen, Charlotte B ; Ørskov, Cathrine ; Larraufie, Pierre ; Kay, Richard G ; Reimann, Frank ; Gribble, Fiona M ; Hartmann, Bolette ; Bojsen-Møller, Kirstine N ; Madsbad, Sten ; Wewer Albrechtsen, Nicolai J ; Holst, Jens J. / Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine. I: International Journal of Obesity. 2020 ; Bind 44, Nr. 9. s. 1859-1871.

Bibtex

@article{522fb050d630449daa039452fe4c77e5,
title = "Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine",
abstract = "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.",
author = "Modvig, {Ida M} and Andersen, {Daniel B} and Grunddal, {Kaare V} and Kuhre, {Rune E} and Christoffer Martinussen and Christiansen, {Charlotte B} and Cathrine {\O}rskov and Pierre Larraufie and Kay, {Richard G} and Frank Reimann and Gribble, {Fiona M} and Bolette Hartmann and Bojsen-M{\o}ller, {Kirstine N} and Sten Madsbad and {Wewer Albrechtsen}, {Nicolai J} and Holst, {Jens J}",
year = "2020",
month = "9",
day = "1",
doi = "10.1038/s41366-020-0541-7",
language = "English",
volume = "44",
pages = "1859--1871",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

AU - Modvig, Ida M

AU - Andersen, Daniel B

AU - Grunddal, Kaare V

AU - Kuhre, Rune E

AU - Martinussen, Christoffer

AU - Christiansen, Charlotte B

AU - Ørskov, Cathrine

AU - Larraufie, Pierre

AU - Kay, Richard G

AU - Reimann, Frank

AU - Gribble, Fiona M

AU - Hartmann, Bolette

AU - Bojsen-Møller, Kirstine N

AU - Madsbad, Sten

AU - Wewer Albrechtsen, Nicolai J

AU - Holst, Jens J

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85079145587&partnerID=8YFLogxK

U2 - 10.1038/s41366-020-0541-7

DO - 10.1038/s41366-020-0541-7

M3 - Journal article

VL - 44

SP - 1859

EP - 1871

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 9

ER -

ID: 59245829