ArticleJournal of molecular medicine (Berlin, Germany)2012
Hyperinsulinemia reduces osteoblast activity in vitro via upregulation of TGF-β.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Opportunities and Risks of Promoting Skin and Bone Healing via Implant Biofunctionalization of Extracellular Matrix Protein ECM1.Journal of functional biomaterials · 2025Review
- Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?Frontiers in dental medicine · 2024Review
- Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.Biomedicines · 2023Review
- Insulin Can Delay Neutrophil Extracellular Trap Formation In Vitro-Implication for Diabetic Wound Care?Biology · 2023Article
- The role of microRNAs in pathophysiology and diagnostics of metabolic complications in obstructive sleep apnea patients.Frontiers in molecular neuroscience · 2023Review
- Adipose Tissue Dysfunction: Impact on Bone and Osseointegration.Calcified tissue international · 2022Review
- A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation.Journal of materials science. Materials in medicine · 2021Article
- Altered Secretome of Diabetic Monocytes Could Negatively Influence Fracture Healing-An In Vitro Study.International journal of molecular sciences · 2021Article
- 3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics.International journal of molecular sciences · 2021Article
- Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models.Archives of toxicology · 2020Review
- Article
- From the Clinical Problem to the Basic Research-Co-Culture Models of Osteoblasts and Osteoclasts.International journal of molecular sciences · 2018Review
- Regulation of Glucose Handling by the Skeleton: Insights From Mouse and Human Studies.Diabetes · 2016Review
- Article
- Osteocalcin, under-carboxylated osteocalcin and osteopontin are not associated with gestational diabetes mellitus but are inversely associated with leptin in non-diabetic women.Journal of endocrinological investigation · 2015Article
- High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure.International journal of molecular sciences · 2015Article
- Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.Langenbeck's archives of surgery · 2014Article
- Negative influence of a long-term high-fat diet on murine bone architecture.International journal of endocrinology · 2014Article
- Anti-diabetic treatment regulates pro-fibrotic TGF-β serum levels in type 2 diabetics.Diabetology & metabolic syndrome · 2013Article
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7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Affecting more than 230,000,000 patients, diabetes mellitus is one of the most frequent metabolic disorders in developed countries. Among other complications, diabetic patients have an increased fracture risk and show delayed fracture healing. During the disease progression, these patients' blood glucose and insulin levels vary significantly. Thus, the aim of this study was to analyze the effects of glucose and insulin on primary human osteoblasts. Although, in the presence of insulin and glucose, proliferation of osteoblasts was increased (1.2- to 1.7-fold), their alkaline phosphatase activity and, consequently, production of mineralized matrix were significantly reduced down to 55 % as compared to control cells (p < 0.001). Interestingly, the observed effects were mainly due to stimulation with insulin. Increase in glucose did not alter osteoblasts' function significantly but further enhanced the effects of insulin. Expression of active and total transforming growth factor beta (TGF-β) was increased by glucose and insulin. Stimulation with both glucose and insulin induced gene expression changes (e.g., osteocalcin, Runx2, Satb2, or Stat1) comparable to treatment with recombinant TGF-β(1), further indicating osteoblasts' dysfunction. Inhibition of TGF-β signaling completely abolished the negative effects of glucose and insulin. In summary, glucose and insulin treatment causes osteoblast dysfunction, which is accompanied by an increased TGF-β expression. Blocking TGF-β signaling abrogates the functional loss observed in glucose- and insulin-treated osteoblasts, thus identifying TGF-β as a key regulator. Therefore, increased TGF-β expression during diabetes may be a feasible pathogenic mechanism underlying poor bone formation in uncontrolled diabetes mellitus.
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