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Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism
Open accessAbstract
The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.
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“OCN promoted the survival and function of pancreatic β-cells and increased insulin secretion [209], while insulin itself induced the release of OCN [210].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [210]
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“Moreover, IL-6 increases production of OCN by osteoblasts [71] (2c), which itself stimulates transient pancreatic secretion of the anorexic hormone insulin and triggers a positive feed-forward mechanism that results in increased OCN and thus more insulin [28,209,210] (2d).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [210]
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Metadata
- Authors
- Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., Ducy, P., & Karsenty, G.
- Affiliations
- Columbia University (US)
- Harvard University (US)
- University of L'Aquila (IT)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 142
- Issue
- 2
- Pages
- 296-308
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2910411
- OpenAlex
- W1971400919
- Cited by
- 1,123
- References
- 49
- Citations by year
- 2026: 30 · 2025: 47 · 2024: 50 · 2023: 41 · 2022: 43 · 2021: 62 · 2020: 84 · 2019: 65 · 2018: 73 · 2017: 89 · 2016: 75 · 2015: 100 · 2014: 76 · 2013: 84 · 2012: 87
- FWCI
- 37.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078042)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045548)
- 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 › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- insulin signaling, osteoblasts, osteocalcin, bone remodeling, bone resorption, glucose homeostasis, energy metabolism, uncarboxylated osteocalcin, decarboxylation, osteoclasts, feed-forward loop
- MeSH terms
- Animals, Cells, Cultured, Energy Metabolism, Extracellular Matrix, Glucose, Humans, Insulin, Mice, Inbred C57BL, Osteoblasts, Signal Transduction, Osteocalcin, Bone Remodeling, Mice
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