Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes

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Standard

Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes. / Kizilkaya, Hüsün Sheyma; Sørensen, Kimmie Vestergaard; Kibsgaard, Camilla J.; Gasbjerg, Laerke Smidt; Hauser, Alexander S.; Sparre-Ulrich, Alexander Hovard; Grarup, Niels; Rosenkilde, Mette M.

I: Frontiers in Cell and Developmental Biology, Bind 9, 749607, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kizilkaya, HS, Sørensen, KV, Kibsgaard, CJ, Gasbjerg, LS, Hauser, AS, Sparre-Ulrich, AH, Grarup, N & Rosenkilde, MM 2021, 'Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes', Frontiers in Cell and Developmental Biology, bind 9, 749607. https://doi.org/10.3389/fcell.2021.749607

APA

Kizilkaya, H. S., Sørensen, K. V., Kibsgaard, C. J., Gasbjerg, L. S., Hauser, A. S., Sparre-Ulrich, A. H., Grarup, N., & Rosenkilde, M. M. (2021). Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes. Frontiers in Cell and Developmental Biology, 9, [749607]. https://doi.org/10.3389/fcell.2021.749607

Vancouver

Kizilkaya HS, Sørensen KV, Kibsgaard CJ, Gasbjerg LS, Hauser AS, Sparre-Ulrich AH o.a. Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes. Frontiers in Cell and Developmental Biology. 2021;9. 749607. https://doi.org/10.3389/fcell.2021.749607

Author

Kizilkaya, Hüsün Sheyma ; Sørensen, Kimmie Vestergaard ; Kibsgaard, Camilla J. ; Gasbjerg, Laerke Smidt ; Hauser, Alexander S. ; Sparre-Ulrich, Alexander Hovard ; Grarup, Niels ; Rosenkilde, Mette M. / Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes. I: Frontiers in Cell and Developmental Biology. 2021 ; Bind 9.

Bibtex

@article{ebc71444a16240239f928d74844c6f59,
title = "Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes",
abstract = "Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR) are involved in multiple physiological systems related to glucose metabolism, bone homeostasis and fat deposition. Recent research has surprisingly indicated that both agonists and antagonists of GIPR may be useful in the treatment of obesity and type 2 diabetes, as both result in weight loss when combined with GLP-1 receptor activation. To understand the receptor signaling related with weight loss, we examined the pharmacological properties of two rare missense GIPR variants, R190Q (rs139215588) and E288G (rs143430880) linked to lower body mass index (BMI) in carriers. At the molecular and cellular level, both variants displayed reduced G protein coupling, impaired arrestin recruitment and internalization, despite maintained high GIP affinity. The physiological phenotyping revealed an overall impaired bone strength, increased systolic blood pressure, altered lipid profile, altered fat distribution combined with increased body impedance in human carriers, thereby substantiating the role of GIP in these physiological processes.",
keywords = "altered receptor signaling and internalization, blood pressure, bone mineral density, glucose-dependent insulinotropic polypeptide receptor (GIPR), gut-bone axis, lipids, single nucleotide variants (SNVs), type 2 diabetes and adiposity",
author = "Kizilkaya, {H{\"u}s{\"u}n Sheyma} and S{\o}rensen, {Kimmie Vestergaard} and Kibsgaard, {Camilla J.} and Gasbjerg, {Laerke Smidt} and Hauser, {Alexander S.} and Sparre-Ulrich, {Alexander Hovard} and Niels Grarup and Rosenkilde, {Mette M.}",
year = "2021",
doi = "10.3389/fcell.2021.749607",
language = "English",
volume = "9",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media",

}

RIS

TY - JOUR

T1 - Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes

AU - Kizilkaya, Hüsün Sheyma

AU - Sørensen, Kimmie Vestergaard

AU - Kibsgaard, Camilla J.

AU - Gasbjerg, Laerke Smidt

AU - Hauser, Alexander S.

AU - Sparre-Ulrich, Alexander Hovard

AU - Grarup, Niels

AU - Rosenkilde, Mette M.

PY - 2021

Y1 - 2021

N2 - Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR) are involved in multiple physiological systems related to glucose metabolism, bone homeostasis and fat deposition. Recent research has surprisingly indicated that both agonists and antagonists of GIPR may be useful in the treatment of obesity and type 2 diabetes, as both result in weight loss when combined with GLP-1 receptor activation. To understand the receptor signaling related with weight loss, we examined the pharmacological properties of two rare missense GIPR variants, R190Q (rs139215588) and E288G (rs143430880) linked to lower body mass index (BMI) in carriers. At the molecular and cellular level, both variants displayed reduced G protein coupling, impaired arrestin recruitment and internalization, despite maintained high GIP affinity. The physiological phenotyping revealed an overall impaired bone strength, increased systolic blood pressure, altered lipid profile, altered fat distribution combined with increased body impedance in human carriers, thereby substantiating the role of GIP in these physiological processes.

AB - Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR) are involved in multiple physiological systems related to glucose metabolism, bone homeostasis and fat deposition. Recent research has surprisingly indicated that both agonists and antagonists of GIPR may be useful in the treatment of obesity and type 2 diabetes, as both result in weight loss when combined with GLP-1 receptor activation. To understand the receptor signaling related with weight loss, we examined the pharmacological properties of two rare missense GIPR variants, R190Q (rs139215588) and E288G (rs143430880) linked to lower body mass index (BMI) in carriers. At the molecular and cellular level, both variants displayed reduced G protein coupling, impaired arrestin recruitment and internalization, despite maintained high GIP affinity. The physiological phenotyping revealed an overall impaired bone strength, increased systolic blood pressure, altered lipid profile, altered fat distribution combined with increased body impedance in human carriers, thereby substantiating the role of GIP in these physiological processes.

KW - altered receptor signaling and internalization

KW - blood pressure

KW - bone mineral density

KW - glucose-dependent insulinotropic polypeptide receptor (GIPR)

KW - gut-bone axis

KW - lipids

KW - single nucleotide variants (SNVs)

KW - type 2 diabetes and adiposity

U2 - 10.3389/fcell.2021.749607

DO - 10.3389/fcell.2021.749607

M3 - Journal article

C2 - 34760890

AN - SCOPUS:85118704362

VL - 9

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 749607

ER -

ID: 284901616