Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans
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Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. / Nissen, Anne; Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina; Holst, Jens Juul; Hartmann, Bolette.
I: The Journal of clinical endocrinology and metabolism, Bind 99, Nr. 11, 11.2014, s. E2325-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans
AU - Nissen, Anne
AU - Christensen, Mikkel
AU - Knop, Filip K
AU - Vilsbøll, Tina
AU - Holst, Jens Juul
AU - Hartmann, Bolette
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Adult
KW - Biological Markers
KW - Blood Glucose
KW - Bone Resorption
KW - Bone and Bones
KW - Collagen Type I
KW - Fasting
KW - Gastric Inhibitory Polypeptide
KW - Glucose Clamp Technique
KW - Humans
KW - Hyperglycemia
KW - Male
KW - Peptides
KW - Young Adult
U2 - 10.1210/jc.2014-2547
DO - 10.1210/jc.2014-2547
M3 - Journal article
C2 - 25144635
VL - 99
SP - E2325-9
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -
ID: 132047356