ArticleActa pharmacologica Sinica2020
Uncarboxylated osteocalcin ameliorates hepatic glucose and lipid metabolism in KKAy mice via activating insulin signaling pathway.
Article in Acta pharmacologica Sinica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- The liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention.Science China. Life sciences · 2026Review
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- Bone as an endocrine regulator of lipid and energy metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- [Liver-bone axis: novel mechanisms and strategies for MAFLD regulation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- The contested association between MASLD and osteoporosis: a narrative review of heterogeneous evidence and modifying factors.Archives of osteoporosis · 2026Review
- The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025Review
- Chrysanthemum morifolium extract improves metabolic dysfunction-associated fatty liver disease by regulating lipid metabolism.Scientific reports · 2025Article
- Proteomic Profiling Reveals Novel Molecular Insights into Dysregulated Proteins in Established Cases of Rheumatoid Arthritis.Proteomes · 2025Article
- Mediating effect of osteocalcin underlying the link between insulin-like growth factor-I and gestational diabetes mellitus.BMC pregnancy and childbirth · 2025Article
- Research Progress on the Influence of Novel Targeted Drugs for Osteoporosis on Glucose Metabolism.Biomolecules · 2025Review
- Osteocalcin and GPR158: linking bone and brain function.Frontiers in cell and developmental biology · 2025Review
- Osteokines in Nonalcoholic Fatty Liver Disease.Current obesity reports · 2024Review
- Roles of osteocalcin in the central nervous system.CNS neuroscience & therapeutics · 2024Review
- Chemically synthesized osteocalcin alleviates NAFLD via the AMPK-FOXO1/BCL6-CD36 pathway.Journal of translational medicine · 2024Article
- Review
- Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- GPR37 and its neuroprotective mechanisms: bridging osteocalcin signaling and brain function.Frontiers in cell and developmental biology · 2024Review
- A trend of osteocalcin in diabetes mellitus research: bibliometric and visualization analysis.Frontiers in endocrinology · 2024Article
- Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation.Molecules (Basel, Switzerland) · 2023Article
- Age- and sex-specific differences in the association of serum osteocalcin and cardiometabolic risk factors in type 2 diabetes.Diabetology & metabolic syndrome · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteocalcin, expressed in osteoblasts of the bone marrow, undergoes post-translational carboxylation and deposits in mineralized bone matrix. A portion of osteocalcin remains uncarboxylated (uncarboxylated osteocalcin, GluOC) that is released into blood where it functions as a hormone to regulate insulin secretion and insulin sensitivity. As insulin resistance is closely associated with metabolic syndrome, this study is aimed to elucidate how GluOC regulates glucose and lipid metabolism in KKAy mice, an animal model displaying obese, hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. GluOC (3, 30 ng/g per day, ig) was orally administered to female KKAy mice for 4 weeks. Whole-body insulin sensitivity, glucose metabolism, hepatic steatosis, dyslipidemia were examined using routine laboratory assays. We found that GluOC administration significantly enhanced insulin sensitivity in KKAy mice by activating hepatic IRβ/PI3K/Akt pathway and elevated the whole-body insulin sensitivity with decreased FPI and HOMA-IR index. Furthermore, GluOC administration alleviated hyperglycemia through suppressing gluconeogenesis and promoting glycogen synthesis in KKAy mice and in cultured hepatocytes in vitro. Moreover, GluOC administration dose-dependently ameliorated dyslipidemia and attenuated hepatic steatosis in KKAy mice by inhibiting hepatic de novo lipogenesis and promoting fatty-acid β-oxidation. These results demonstrate that GluOC effectively enhances hepatic insulin sensitivity, improves hyperglycemia and ameliorates hepatic steatosis in KKAy mice, suggesting that GluOC could be a promising drug candidate for treating metabolic syndrome.
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