Gastric Inhibitory Polypeptide as an Endogenous Factor Promoting New Bone Formation after Food Ingestion
Open accessAbstract
Calcium plays a fundamental role as second messenger in intracellular signaling and bone serves as the body’s calcium reserve to tightly maintain blood calcium levels. Calcium in ingested meal is the main supply and inadequate calcium intake causes osteoporosis and bone fracture. Here, we describe a novel mechanism of how ingested calcium is deposited on bone. Meal ingestion elicits secretion of the gut hormone gastric inhibitory polypeptide (GIP) from endocrine K cells in the duodenum. Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR−/−) were significantly lower than those of wild-type (GIPR+/+) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR−/− mice, indicating that GIPR−/− mice have high-turnover osteoporosis. In vitro examination showed the percentage of osteoblastic cells undergoing apoptosis to be significantly decreased in the presence of GIP. Because GIPR−/− mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone.
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GIP stimulates bone formation by inhibiting osteoclast apoptosis.
“GIP also stimulates bone formation by inhibiting osteoclast apoptosis [52].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [52]
The ‘Antiapoptotic Effect of GIP on Osteoblasts’ section reports that GIP prevented apoptosis of osteoblasts, not osteoclasts. The ‘No Direct Effect of GIP on Osteoclasts’ section says GIP did not directly inhibit osteoclast function. The claim names the wrong cell type for the reported antiapoptotic effect. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredLiraglutide specifically reduces bone resorption without influencing bone formation.
“These findings suggest that liraglutide specifically reduces bone resorption without influencing bone formation.368”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [368]
The section on inhibition of GIP signaling reports changes in both bone formation and resorption in GIP-receptor-deficient mice. The Discussion also concerns GIP, not liraglutide. Searches for liraglutide and for a reduction in resorption without an effect on formation found no passage addressing the claimed drug effect; page numbers were unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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- Authors
- Tsukiyama, K., Yamada, Y., Yamada, C., Harada, N., Kawasaki, Y., Ogura, M., Bessho, K., Li, M., Amizuka, N., Sato, M., Udagawa, N., Takahashi, N., Tanaka, K., Oiso, Y., & Seino, Y.
- Affiliations
- Nagoya University (JP)
- Departments of Diabetes and Clinical Nutrition (K.Ts., Y.Y., C.Y., N.H., Y.K., M.O., Y.S.), Kyoto 606-8507, Japan;
- Kyoto University (JP)
- Niigata University (JP)
- Department of Biochemistry (M.S., N.U.), Nagano 399-0781, Japan;
- Matsumoto Dental University (JP)
- Kyoto Women's University (JP)
- Kansai Electric Power Hospital (JP)
- Corresponding author
- Yamada, Yuichiro
- ORCID
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-07-01
- Volume
- 20
- Issue
- 7
- Pages
- 1644-1651
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2103318165
- Cited by
- 198
- References
- 33
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 17 · 2018: 15 · 2017: 11 · 2016: 12 · 2015: 15 · 2014: 12 · 2013: 18 · 2012: 6
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- glucose-dependent insulinotropic polypeptide, GIP receptor, bone formation, calcium homeostasis, meal ingestion, gastrointestinal hormones, K cells, osteoclasts, osteoblast apoptosis, plasma calcium, bone histomorphometry
- MeSH terms
- Animals, Bone Resorption, Calcium, Eating, Gastric Inhibitory Polypeptide, Male, Mice, Transgenic, Models, Biological, Osteoblasts, Osteoclasts, Osteogenesis, Osteoporosis, Tibia, Signal Transduction, Apoptosis Regulatory Proteins, Mice
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