TY - JOUR

T1 - The role of endogenous GIP and GLP-1 in postprandial bone homeostasis

AU - Helsted, Mads M.

AU - Gasbjerg, Lærke S.

AU - Lanng, Amalie R.

AU - Bergmann, Natasha C.

AU - Stensen, Signe

AU - Hartmann, Bolette

AU - Christensen, Mikkel B.

AU - Holst, Jens J.

AU - Vilsbøll, Tina

AU - Rosenkilde, Mette M.

AU - Knop, Filip K.

PY - 2020

Y1 - 2020

N2 - The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies. We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20–70), BMI 27.2 (22.4–37.0) kg/m2) or liquid mixed meal tests (MMTs) (n = 12, age 23 (19–65), BMI 23.7 (20.3–25.5) kg/m2) with infusions of 1) the GIP receptor antagonist GIP(3-30)NH2, 2) the GLP-1 receptor antagonist exendin(9–39)NH2, 3) both GIP(3–30)NH2 and exendin(9–39)NH2, or 4) placebo infusions (saline) on four separate visits. Bone resorption was evaluated from levels of circulating carboxy-terminal collagen crosslinks (CTX) and bone formation from levels of procollagen type 1 amino-terminal propeptide (P1NP). During placebo infusions, baseline-subtracted area under the curve values for CTX were −39 ± 5.0 (OGTT) and −57 ± 4.3 ng/ml × min (MMT). When GIP(3–30)NH2 was administered, CTX suppression was significantly diminished compared to placebo (−30 ± 4.8 (OGTT) and −45 ± 4.6 ng/ml × min (MMT), P = 0.0104 and P = 0.0288, respectively, compared to placebo. During exendin(9–39)NH2 infusion, CTX suppression after OGTT/MMT was similar to placebo (P = 0.28 (OGTT) and P = 0.93 (MMT)). The relative contribution of endogenous GIP to postprandial suppression of bone resorption during both OGTT and MMT was similar and reached 22–25%. There were no differences in P1NP concentrations between interventions. In conclusion, endogenous GIP contributes by up to 25% to postprandial suppression of bone resorption in humans whereas an effect of endogenous GLP-1 could not be demonstrated.

AB - The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies. We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20–70), BMI 27.2 (22.4–37.0) kg/m2) or liquid mixed meal tests (MMTs) (n = 12, age 23 (19–65), BMI 23.7 (20.3–25.5) kg/m2) with infusions of 1) the GIP receptor antagonist GIP(3-30)NH2, 2) the GLP-1 receptor antagonist exendin(9–39)NH2, 3) both GIP(3–30)NH2 and exendin(9–39)NH2, or 4) placebo infusions (saline) on four separate visits. Bone resorption was evaluated from levels of circulating carboxy-terminal collagen crosslinks (CTX) and bone formation from levels of procollagen type 1 amino-terminal propeptide (P1NP). During placebo infusions, baseline-subtracted area under the curve values for CTX were −39 ± 5.0 (OGTT) and −57 ± 4.3 ng/ml × min (MMT). When GIP(3–30)NH2 was administered, CTX suppression was significantly diminished compared to placebo (−30 ± 4.8 (OGTT) and −45 ± 4.6 ng/ml × min (MMT), P = 0.0104 and P = 0.0288, respectively, compared to placebo. During exendin(9–39)NH2 infusion, CTX suppression after OGTT/MMT was similar to placebo (P = 0.28 (OGTT) and P = 0.93 (MMT)). The relative contribution of endogenous GIP to postprandial suppression of bone resorption during both OGTT and MMT was similar and reached 22–25%. There were no differences in P1NP concentrations between interventions. In conclusion, endogenous GIP contributes by up to 25% to postprandial suppression of bone resorption in humans whereas an effect of endogenous GLP-1 could not be demonstrated.

KW - Bone metabolism

KW - Bone resorption

KW - CTX

KW - Exendin(9–39)NH

KW - GIP(3–30)NH

KW - Glucagon-like peptide 1

KW - Glucose-dependent insulinotropic polypeptide

KW - Gut-bone axis

KW - Incretin hormones

U2 - 10.1016/j.bone.2020.115553

DO - 10.1016/j.bone.2020.115553

M3 - Journal article

C2 - 32730920

AN - SCOPUS:85089266119

VL - 140

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 115553

ER -