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Glucose-dependent Insulinotropic Polypeptide Inhibits Bone Resorption in Humans

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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 anti-resorptive 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 4 conditions: euglycemic (5 mmol/L) and hyperglycemic (12 mmol/L) 90 min 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 analysed for concentrations of degradation products of C-terminal telopeptides 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 curve (AUC) in CTX was significantly (P<0.001) higher during GIP infusion (2084±686 %×min) compared to saline infusion (656±295 %×min). During hyperglycemia, GIP infusion significantly (P<0.001) augmented the decremental AUC to 2785±446 %×min compared to 1308±448 %×min 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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Pages (from-to)jc20142547
ISSN0021-972X
DOIs
Publication statusPublished - 21 Aug 2014

ID: 44521636