Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans

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 - 2014/11/1

Y1 - 2014/11/1

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

SN - 0021-972X

VL - 99

SP - E2325-9

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 11

ER -