The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Zhou, Qiyun; Guan, Zhiqiang; Liu, Shengfu; Xuan, Yan-jiao; Han, Gang; Chen, Hua; Jin, Xiao; Tao, Kun; Guan, Zhiyuan

doi:10.18632/aging.203729

Cited by 18 publications

(8 citation statements)

References 62 publications

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“…Balaji et al [40] found that alendronate can reduce the risk of type 2 diabetes in the Indian population. Previous population-based cohort studies have also found that bisphosphonate exposure is related to a decreased risk of type 2 diabetes [39,41], but the clear mechanism of action between the two remains unclear.…”

Section: Discussionmentioning

confidence: 98%

“…Compared with the first two generations of drugs, it has stronger anti-bone resorption and no bone mineralization inhibition [38]. Zhou et al [39] observed that in C57BL mice, the use of alendronate alone can significantly increase serum glucagon-like peptide-1 levels compared with the diabetes group. Balaji et al [40] found that alendronate can reduce the risk of type 2 diabetes in the Indian population.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

Yang,

Jin

2024

Horm Metab Res

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The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05–0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01–0.11); Ward’s triangle BMD increased 0.07 g/cm² (95% CI: 0.04–0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04–0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18–2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: –1.81–0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: –0.07; 95% CI: –1.12–1.25), serum calcium (MD: 0.01; 95% CI: –0.03–0.04), serum phosphorus (MD: 0.04; 95% CI: –0.03–0.10) and medication safety (OR: 1.75; 95% CI: 1.29–2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

Yang,

Jin

2024

Horm Metab Res

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“…The levels of expression of bone metabolisms, glucose metabolism, and inflammation‐related genes, such as Endothelial PAS Domain Protein 1 (EPAS1), Transmenbrane glycoprotein mucin1 (MUC1), CD44 Molecule (CD44), SLC2A1, Cyclin‐Dependent Kinase Inhibitor 1A (CDKN1A), and Dual Specificity Phosphatase 1 (DUSP1), have been uploaded in Table S1 . With the Sham group as the baseline, the mRNA of on‐related genes such as EPAS1, MUC1, CD44, SLC2A1, CDKN1A, and DUSP1 is computed (Zhou et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF‐1α to inhibit knee osteoarthritis‐induced ferroptosis

et al. 2023

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Ferroptosis is an iron‐dependent cell death that has been found to aggravate the progression of osteoarthritis (OA) and gut microbiota‐ OA axis refers to the bidirectional information network between the gut microbiota and OA, which may provide a new way to protect the OA. However, the role of gut microbiota‐derived metabolites in ferroptosis‐relative osteoarthritis remains unclear. The objective of this study was to analyze the protective effect of gut microbiota and its metabolite capsiate (CAT) on ferroptosis‐relative osteoarthritis in vivo and in vitro experiments. From June 2021 to February 2022, 78 patients were evaluated retrospectively and divided into two groups: The health group (n = 39) and the OA group (n = 40). Iron and oxidative stress indicators were determined in peripheral blood samples. And then in vivo and in vitro experiments, a surgically destabilized medial meniscus (DMM) mice model was established and treated with CAT or Ferric Inhibitor‐1 (Fer‐1). Solute Carrier Family 2 Member 1 (SLC2A1) short hairpin RNA (shRNA) was utilized to inhibit SLC2A1 expression. Serum iron was increased significantly but total iron binding capacity was decreased significantly in OA patients than healthy people (p < 0.0001). The least absolute shrinkage and selection operator clinical prediction model suggested that serum iron, total iron binding capacity, transferrin, and superoxide dismutase were all independent predictors of OA (p < 0.001). Bioinformatics results suggested that SLC2A1, Metastasis‐Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and HIF‐1α (Hypoxia Inducible Factor 1 Alpha)‐related oxidative stress signaling pathways play an important role in iron homeostasis and OA. In addition, gut microbiota 16s RNA sequencing and untargeted metabolomics were used to find that gut microbiota metabolites CAT in mice with osteoarthritis were negatively correlated with Osteoarthritis Research Society International (OARSI) scores for chondrogenic degeneration (p = 0.0017). Moreover, CAT reduced ferroptosis‐dependent osteoarthritis in vivo and in vitro. However, the protective effect of CAT against ferroptosis‐dependent osteoarthritis could be eliminated by silencing SLC2A1. SLC2A1 was upregulated but reduced the SLC2A1 and HIF‐1α levels in the DMM group. HIF‐1α, MALAT1, and apoptosis levels were increased after SLC2A1 knockout in chondrocyte cells (p = 0.0017). Finally, downregulation of SLC2A1 expression by Adeno‐associated Virus (AAV) ‐SLC2A1 shRNA improves osteoarthritis in vivo. Our findings indicated that CAT inhibited HIF‐1a expression and reduced ferroptosis‐relative osteoarthritis progression by activating SLC2A1.

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“…Intraperitoneal Injection of Glucose Tolerance Test (IPGTT): IPGTT was performed in all animals at 8 and 10 weeks of the experiments according to a method as previously described. [40] Briefly, mice were fasted for 12 h before intraperitoneal injection with 20% glucose solution w/w in proportion to the bodyweight (1 g kg −1 body weight). The blood glucose level was measured at 0, 30, 60, 90, and 120 min after the injection.…”

Section: Methodsmentioning

confidence: 99%

Goat Milk Improves Glucose Metabolism in Type 2 Diabetic Mice and Protects Pancreatic β‐Cell Functions

Chen,

Zhang,

Niu

et al. 2023

Molecular Nutrition Food Res

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ScopeConsuming goat milk is known to benefit high‐fat diet‐fed and streptozocin (STZ)‐induced diabetic rats, but the underlying mechanisms are unknown. This study is conducted to investigate the metabolic effects of a goat milk diet (a form of goat milk powder) on glucose homeostasis and pancreatic conditions in a mouse model of Type 2 diabetes mellitus (T2DM) induced by STZ.Methods and resultsT2DM mice are fed with a goat‐milk‐based diet containing 10.3% w/w goat milk powder for 10 weeks for investigating the in vivo effects; a β‐cell line MIN6 cells are used to test the in vitro effects of digested goat milk (DGM). Goat milk diet improves the deleterious effects of STZ on fasting glucose levels and glucose tolerance, accelerates pancreatic structure recovery, and alters blood metabolites in mice. Based on the significant differences observed in metabolites, the key pathways, metabolite regulatory enzymes, metabolite molecular modules, and biochemical reactions are identified as critical integrated pathways. DGM promotes the cell activity, glucose transportation, and AKT activation in cultured STZ‐treated MIN6 cells in vitro.ConclusionsGoat milk diet improves glucose homeostasis and pancreatic conditions of T2DM mice, in association with improved blood metabolite profiles and activation of pancreatic AKT pathway.

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The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Cited by 18 publications

References 62 publications

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF‐1α to inhibit knee osteoarthritis‐induced ferroptosis

Goat Milk Improves Glucose Metabolism in Type 2 Diabetic Mice and Protects Pancreatic β‐Cell Functions

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