title: Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans.
abstract: BACKGROUND
  In humans, the pronounced postprandial reduction in bone resorption (decreasing bone resorption markers by around 50%) has been suggested to be caused by gut hormones. Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone secreted postprandially from the small intestine. The hormone is known as an incretin hormone, but preclinical studies have suggested that it may also influence bone metabolism, showing both antiresorptive and anabolic effects as reflected by changes in biomechanical measures, microarchitecture, and activity of the bone cells in response to GIP stimulation. Its role in human bone homeostasis, however, is unknown.
  
  
  OBJECTIVE
  To examine the effect of GIP administration on bone resorption in humans.
  
  
  METHODS
  Plasma samples were obtained from 10 healthy subjects during four conditions: euglycemic (5 mmol/L) and hyperglycemic (12 mmol/L) 90-minute glucose clamps with co-infusion of GIP (4 pmol/kg/min for 15 min, followed by 2 pmol/kg/min for 45 min) or placebo. The samples were analyzed for concentrations of degradation products of C-terminal telopeptide of type I collagen (CTX), a bone resorption marker. RESULTS regarding effects on pancreatic hormone secretion have been published.
  
  
  RESULTS
  During euglycemia, the decremental area under the curve in CTX was significantly (P < .001) higher during GIP infusion (2084 ± 686 % × min) compared to saline infusion (656 ± 295 % × min). During hyperglycemia, GIP infusion significantly (P < .001) augmented the decremental area under the curve to 2785 ± 446 % × minutes, compared to 1308 ± 448 % × minutes during saline infusion, with CTX values corresponding to 49% of basal values.
  
  
  CONCLUSIONS
  We conclude that GIP reduces bone resorption in humans, interacting with a possible effect of hyperglycemia.
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research (A.N., F.K.K., J.J.H., B.H.), Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; and Center for Diabetes Research (M.C., F.K.K., T.V.), Department of Medicine, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Nissen
authors.forename: Mikkel
authors.initials: M
authors.lastname: Christensen
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001862:Bone Resorption / Q000188:drug therapy*; D001842:Bone and Bones / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood*; D005215:Fasting / Q000097:blood*; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D008297:Male; D010455:Peptides / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D005749:Gastric Inhibitory Polypeptide