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Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control

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Fernandez-Cachon, María L ; Pedersen, Søren L ; Rigbolt, Kristoffer T ; Zhang, Chen ; Fabricius, Katrine ; Hansen, Henrik H ; Elster, Lisbeth ; Fink, Lisbeth N ; Schäfer, Matthias ; Rhee, Nicolai A ; Langholz, Ebbe ; Wandall, Erik ; Friis, Steffen U ; Vilmann, Peter ; Kristiansen, Viggo B ; Schmidt, Christina ; Schreiter, Kay ; Breitschopf, Kristin ; Hübschle, Thomas ; Jorsal, Tina ; Vilsbøll, Tina ; Schmidt, Thorsten ; Theis, Stefan ; Knop, Filip K ; Larsen, Philip Just ; Jelsing, Jacob. / Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control. I: Peptides. 2018 ; Bind 101. s. 32-43.

Bibtex

@article{b00d2f2822f042dfad80a8d2b45abafb,
title = "Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control",
abstract = "AIM: To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB.METHODS: Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas.RESULTS: GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice.CONCLUSION: GN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.",
keywords = "Journal Article",
author = "Fernandez-Cachon, {Mar{\'i}a L} and Pedersen, {S{\o}ren L} and Rigbolt, {Kristoffer T} and Chen Zhang and Katrine Fabricius and Hansen, {Henrik H} and Lisbeth Elster and Fink, {Lisbeth N} and Matthias Sch{\"a}fer and Rhee, {Nicolai A} and Ebbe Langholz and Erik Wandall and Friis, {Steffen U} and Peter Vilmann and Kristiansen, {Viggo B} and Christina Schmidt and Kay Schreiter and Kristin Breitschopf and Thomas H{\"u}bschle and Tina Jorsal and Tina Vilsb{\o}ll and Thorsten Schmidt and Stefan Theis and Knop, {Filip K} and Larsen, {Philip Just} and Jacob Jelsing",
note = "Copyright {\circledC} 2017. Published by Elsevier Inc.",
year = "2018",
month = "3",
doi = "10.1016/j.peptides.2017.12.024",
language = "English",
volume = "101",
pages = "32--43",
journal = "Peptides",
issn = "0196-9781",
publisher = "Elsevier Inc",

}

RIS

TY - JOUR

T1 - Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control

AU - Fernandez-Cachon, María L

AU - Pedersen, Søren L

AU - Rigbolt, Kristoffer T

AU - Zhang, Chen

AU - Fabricius, Katrine

AU - Hansen, Henrik H

AU - Elster, Lisbeth

AU - Fink, Lisbeth N

AU - Schäfer, Matthias

AU - Rhee, Nicolai A

AU - Langholz, Ebbe

AU - Wandall, Erik

AU - Friis, Steffen U

AU - Vilmann, Peter

AU - Kristiansen, Viggo B

AU - Schmidt, Christina

AU - Schreiter, Kay

AU - Breitschopf, Kristin

AU - Hübschle, Thomas

AU - Jorsal, Tina

AU - Vilsbøll, Tina

AU - Schmidt, Thorsten

AU - Theis, Stefan

AU - Knop, Filip K

AU - Larsen, Philip Just

AU - Jelsing, Jacob

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2018/3

Y1 - 2018/3

N2 - AIM: To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB.METHODS: Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas.RESULTS: GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice.CONCLUSION: GN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.

AB - AIM: To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB.METHODS: Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas.RESULTS: GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice.CONCLUSION: GN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.

KW - Journal Article

U2 - 10.1016/j.peptides.2017.12.024

DO - 10.1016/j.peptides.2017.12.024

M3 - Journal article

VL - 101

SP - 32

EP - 43

JO - Peptides

JF - Peptides

SN - 0196-9781

ER -

ID: 52352271