Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism

Morten S S Hansen*, Michaela Tencerova, Jacob Frølich, Moustapha Kassem, Morten Frost

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

15 Downloads (Pure)

Abstract

The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.

Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume122
Issue number1
Pages (from-to)25–37
ISSN1742-7835
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Metabolism
Bone
Incretins
Hormones
Homeostasis
Bone Fractures
Glucagon-Like Peptide-1 Receptor
Glucose
Osteogenesis
Skeleton
Bone Density
Type 2 Diabetes Mellitus
Intestines
Physiology
Rodentia
Medical problems
Cell culture
Clinical Trials

Bibliographical note

© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Keywords

  • Animals
  • Bone Density/drug effects
  • Bone Resorption/chemically induced
  • Bone and Bones/cytology
  • Diabetes Mellitus, Type 2/drug therapy
  • Disease Models, Animal
  • Fractures, Bone/chemically induced
  • Gastric Inhibitory Polypeptide/metabolism
  • Glucagon-Like Peptide 1/metabolism
  • Glucagon-Like Peptide-1 Receptor/agonists
  • Humans
  • Incretins/pharmacology
  • Insulin/metabolism
  • Obesity/drug therapy
  • Osteoblasts/drug effects
  • Osteocalcin/metabolism
  • Osteoclasts/drug effects

Cite this

@article{7df87b29ec93432a815ca480407c7114,
title = "Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism",
abstract = "The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.",
keywords = "Animals, Bone Density/drug effects, Bone Resorption/chemically induced, Bone and Bones/cytology, Diabetes Mellitus, Type 2/drug therapy, Disease Models, Animal, Fractures, Bone/chemically induced, Gastric Inhibitory Polypeptide/metabolism, Glucagon-Like Peptide 1/metabolism, Glucagon-Like Peptide-1 Receptor/agonists, Humans, Incretins/pharmacology, Insulin/metabolism, Obesity/drug therapy, Osteoblasts/drug effects, Osteocalcin/metabolism, Osteoclasts/drug effects",
author = "Hansen, {Morten S S} and Michaela Tencerova and Jacob Fr{\o}lich and Moustapha Kassem and Morten Frost",
note = "{\circledC} 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).",
year = "2018",
month = "1",
doi = "10.1111/bcpt.12850",
language = "English",
volume = "122",
pages = "25–37",
journal = "Basic & Clinical Pharmacology & Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism

AU - Hansen, Morten S S

AU - Tencerova, Michaela

AU - Frølich, Jacob

AU - Kassem, Moustapha

AU - Frost, Morten

N1 - © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

PY - 2018/1

Y1 - 2018/1

N2 - The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.

AB - The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.

KW - Animals

KW - Bone Density/drug effects

KW - Bone Resorption/chemically induced

KW - Bone and Bones/cytology

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Disease Models, Animal

KW - Fractures, Bone/chemically induced

KW - Gastric Inhibitory Polypeptide/metabolism

KW - Glucagon-Like Peptide 1/metabolism

KW - Glucagon-Like Peptide-1 Receptor/agonists

KW - Humans

KW - Incretins/pharmacology

KW - Insulin/metabolism

KW - Obesity/drug therapy

KW - Osteoblasts/drug effects

KW - Osteocalcin/metabolism

KW - Osteoclasts/drug effects

U2 - 10.1111/bcpt.12850

DO - 10.1111/bcpt.12850

M3 - Review

C2 - 28722834

VL - 122

SP - 25

EP - 37

JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7835

IS - 1

ER -