4.6 Article

Subcutaneous GIP and GLP-2 inhibit nightly bone resorption in postmenopausal women: A preliminary study

期刊

BONE
卷 152, 期 -, 页码 -

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2021.116065

关键词

Glucose-dependent insulinotropic polypeptide (GIP); Glucagon-like peptide-2 (GLP-2); Bone turnover; Gut-bone axis; CTX; P1NP

资金

  1. Novo Nordisk Foundation [NNF19OC0056951, NNF18CC0034900]
  2. Novo Nordisk Foundation Center for Basic Metabolic Research
  3. Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center based at the University of Copenhagen, Denmark
  4. Michaelsen Foundation

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In postmenopausal women, both GIP and GLP-2 individually inhibit bone resorption during nighttime, with complementary effects when combined. GIP rapidly reduces CTX levels within 45-120 minutes post-injection, while GLP-2 has a more delayed effect between 120-240 minutes post-injection.
Background: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxyterminal type 1 collagen crosslinks (CTX). Objective: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption. Methods: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP + GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP). Results: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 min after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 min after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 min after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP). Conclusion: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.

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