Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{9574f7c07c894df0b8df5e91f77909f8,
title = "The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery",
abstract = "Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weightloss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. In vitro, incretin release depends on glucose absorption via sodium-glucose cotransporter 1 (SGLT1). We investigated the importance of SGLT1/SGLT2 for enteropancreatic hormone concentrations and glucose metabolism after RYGB in a randomized, controlled, crossover study. Ten RYGB-operated patients ingested 50 g of oral glucose with and without acute pretreatment with 600 mg of the SGLT1/SGLT2-inhibitor canagliflozin. Paracetamol and 3-O-methyl-D-glucopyranose (3-OMG) were added to the glucose drink to evaluate rates of intestinal entry and absorption of glucose, respectively. Blood samples were collected for 4 h. The primary outcome was 4-h plasma GLP-1 (incremental area-under the curve, iAUC). Secondary outcomes included glucose, GIP, insulin, and glucagon. Canagliflozin delayed glucose absorption (time-to-peak 3-OMG: 50 vs. 132 min, P < 0.01) but did not reduce iAUC GLP-1 (6,067 vs. 7,273·min·pmol-1·L-1, P = 0.23), although peak GLP-1 concentrations were lowered (-28%, P = 0.03). Canagliflozin reduced GIP (iAUC -28%, P =0.01; peak concentrations -57%, P < 0.01), insulin, and glucose excursions, whereas plasma glucagon (AUC 3,216 vs. 4,160 min·pmol·L-1, P = 0.02) and amino acids were increased. In conclusion, acute SGLT1/SGLT2-inhibition during glucose ingestion did not reduce 4-h plasma GLP-1 responses in RYGBpatients but attenuated the early rise in GLP-1, GIP, and insulin, whereas late glucagon concentrations were increased. The results suggest that SGLT1-mediated glucose absorption contributes to incretin hormone secretion after RYGB.",
keywords = "glucagon, incretins, obesity, Roux-en-Y gastric bypass, sodium-glucose cotransporter, Incretins, Obesity, Glucagon, Sodium-glucose cotransporter, Gastric Bypass, Pancreatic Polypeptide/drug effects, Humans, Middle Aged, Sodium-Glucose Transporter 1/antagonists & inhibitors, Incretins/metabolism, Canagliflozin/pharmacology, C-Peptide/drug effects, Insulin/metabolism, Sodium-Glucose Transporter 2/metabolism, Sodium-Glucose Transporter 2 Inhibitors/pharmacology, Gastric Inhibitory Polypeptide/drug effects, Glucose Tolerance Test, Glucagon/drug effects, Cross-Over Studies, Blood Glucose/drug effects, Glucagon-Like Peptide 1/drug effects",
author = "Christoffer Martinussen and Simon Veedfald and Carsten Dirksen and Bojsen-M{\o}ller, {Kirstine N} and Svane, {Maria S} and {Wewer Albrechtsen}, {Nicolai J} and {van Hall}, Gerrit and Kristiansen, {Viggo B} and Mogens Fenger and Holst, {Jens J} and Sten Madsbad",
year = "2020",
month = jun,
day = "1",
doi = "10.1152/ajpendo.00023.2020",
language = "English",
volume = "318",
pages = "E956--E964",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "6",

}

RIS

TY - JOUR

T1 - The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

AU - Martinussen, Christoffer

AU - Veedfald, Simon

AU - Dirksen, Carsten

AU - Bojsen-Møller, Kirstine N

AU - Svane, Maria S

AU - Wewer Albrechtsen, Nicolai J

AU - van Hall, Gerrit

AU - Kristiansen, Viggo B

AU - Fenger, Mogens

AU - Holst, Jens J

AU - Madsbad, Sten

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weightloss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. In vitro, incretin release depends on glucose absorption via sodium-glucose cotransporter 1 (SGLT1). We investigated the importance of SGLT1/SGLT2 for enteropancreatic hormone concentrations and glucose metabolism after RYGB in a randomized, controlled, crossover study. Ten RYGB-operated patients ingested 50 g of oral glucose with and without acute pretreatment with 600 mg of the SGLT1/SGLT2-inhibitor canagliflozin. Paracetamol and 3-O-methyl-D-glucopyranose (3-OMG) were added to the glucose drink to evaluate rates of intestinal entry and absorption of glucose, respectively. Blood samples were collected for 4 h. The primary outcome was 4-h plasma GLP-1 (incremental area-under the curve, iAUC). Secondary outcomes included glucose, GIP, insulin, and glucagon. Canagliflozin delayed glucose absorption (time-to-peak 3-OMG: 50 vs. 132 min, P < 0.01) but did not reduce iAUC GLP-1 (6,067 vs. 7,273·min·pmol-1·L-1, P = 0.23), although peak GLP-1 concentrations were lowered (-28%, P = 0.03). Canagliflozin reduced GIP (iAUC -28%, P =0.01; peak concentrations -57%, P < 0.01), insulin, and glucose excursions, whereas plasma glucagon (AUC 3,216 vs. 4,160 min·pmol·L-1, P = 0.02) and amino acids were increased. In conclusion, acute SGLT1/SGLT2-inhibition during glucose ingestion did not reduce 4-h plasma GLP-1 responses in RYGBpatients but attenuated the early rise in GLP-1, GIP, and insulin, whereas late glucagon concentrations were increased. The results suggest that SGLT1-mediated glucose absorption contributes to incretin hormone secretion after RYGB.

AB - Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weightloss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. In vitro, incretin release depends on glucose absorption via sodium-glucose cotransporter 1 (SGLT1). We investigated the importance of SGLT1/SGLT2 for enteropancreatic hormone concentrations and glucose metabolism after RYGB in a randomized, controlled, crossover study. Ten RYGB-operated patients ingested 50 g of oral glucose with and without acute pretreatment with 600 mg of the SGLT1/SGLT2-inhibitor canagliflozin. Paracetamol and 3-O-methyl-D-glucopyranose (3-OMG) were added to the glucose drink to evaluate rates of intestinal entry and absorption of glucose, respectively. Blood samples were collected for 4 h. The primary outcome was 4-h plasma GLP-1 (incremental area-under the curve, iAUC). Secondary outcomes included glucose, GIP, insulin, and glucagon. Canagliflozin delayed glucose absorption (time-to-peak 3-OMG: 50 vs. 132 min, P < 0.01) but did not reduce iAUC GLP-1 (6,067 vs. 7,273·min·pmol-1·L-1, P = 0.23), although peak GLP-1 concentrations were lowered (-28%, P = 0.03). Canagliflozin reduced GIP (iAUC -28%, P =0.01; peak concentrations -57%, P < 0.01), insulin, and glucose excursions, whereas plasma glucagon (AUC 3,216 vs. 4,160 min·pmol·L-1, P = 0.02) and amino acids were increased. In conclusion, acute SGLT1/SGLT2-inhibition during glucose ingestion did not reduce 4-h plasma GLP-1 responses in RYGBpatients but attenuated the early rise in GLP-1, GIP, and insulin, whereas late glucagon concentrations were increased. The results suggest that SGLT1-mediated glucose absorption contributes to incretin hormone secretion after RYGB.

KW - glucagon

KW - incretins

KW - obesity

KW - Roux-en-Y gastric bypass

KW - sodium-glucose cotransporter

KW - Incretins

KW - Obesity

KW - Glucagon

KW - Sodium-glucose cotransporter

KW - Gastric Bypass

KW - Pancreatic Polypeptide/drug effects

KW - Humans

KW - Middle Aged

KW - Sodium-Glucose Transporter 1/antagonists & inhibitors

KW - Incretins/metabolism

KW - Canagliflozin/pharmacology

KW - C-Peptide/drug effects

KW - Insulin/metabolism

KW - Sodium-Glucose Transporter 2/metabolism

KW - Sodium-Glucose Transporter 2 Inhibitors/pharmacology

KW - Gastric Inhibitory Polypeptide/drug effects

KW - Glucose Tolerance Test

KW - Glucagon/drug effects

KW - Cross-Over Studies

KW - Blood Glucose/drug effects

KW - Glucagon-Like Peptide 1/drug effects

UR - http://www.scopus.com/inward/record.url?scp=85086051750&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00023.2020

DO - 10.1152/ajpendo.00023.2020

M3 - Journal article

C2 - 32182123

VL - 318

SP - E956-E964

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 6

ER -

ID: 59613750