Anne Nissen1, Mikkel Christensen, Filip K Knop, Tina Vilsbøll, Jens J Holst, Bolette Hartmann. 1. 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.
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. MATERIALS AND 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.
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. MATERIALS AND 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: Lærke S Gasbjerg; Mikkel B Christensen; Bolette Hartmann; Amalie R Lanng; Alexander H Sparre-Ulrich; Maria B N Gabe; Flemming Dela; Tina Vilsbøll; Jens J Holst; Mette M Rosenkilde; Filip K Knop Journal: Diabetologia Date: 2017-09-25 Impact factor: 10.122
Authors: Kaisa K Ivaska; Maikki K Heliövaara; Pertti Ebeling; Marco Bucci; Ville Huovinen; H Kalervo Väänänen; Pirjo Nuutila; Heikki A Koistinen Journal: Endocr Connect Date: 2015-06-05 Impact factor: 3.335
Authors: L S Hansen; A H Sparre-Ulrich; M Christensen; F K Knop; B Hartmann; J J Holst; M M Rosenkilde Journal: Br J Pharmacol Date: 2016-01-30 Impact factor: 8.739