scholarly journals Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis

2004 ◽  
Vol 183 (1) ◽  
pp. 203-216 ◽  
Author(s):  
M Alexandra Sorocéanu ◽  
Dengshun Miao ◽  
Xiu-Ying Bai ◽  
Hanyi Su ◽  
David Goltzman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Serum Levels ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Apoptotic Death ◽  
Rosiglitazone Treatment

Thiazolidinediones (TZDs) increase peripheral tissue insulin sensitivity in patients with type 2 diabetes mellitus by activating the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). In bone marrow stromal cell cultures and in vivo, activation of PPARγ by high doses (20 mg/kg/day) of TZDs has been reported to alter stem cell differentiation by promoting commitment of progenitor cells to the adipocytic lineage while inhibiting osteoblastogenesis. Here, we have examined the in vivo effects of low-dose rosiglitazone (3 mg/kg/day) on bone, administered to mice by gavage for 90 days. Rosiglitazone-treated mice had increased weight when compared with controls, with no significant alterations in serum levels of glucose, calcium or parathyroid hormone (PTH). Bone mineral density (BMD) at the lumbar vertebrae (L1–L4), ilium/sacrum, and total body was diminished by rosiglitazone treatment. Histologically, bone was characterized by decreased trabecular bone volume and increased marrow space with no significant change in bone marrow adipocity. Decreased osteoblast number and activity due to increased apoptotic death of osteoblasts and osteocytes was apparent while osteoclast parameters and serum levels of osteocalcin, alkaline phosphatase activity, and leptin were unaltered by rosiglitazone treatment. Therefore, the imbalance in bone remodeling that follows rosiglitazone administration arises from increased apoptotic death of osteogenic cells and diminished bone formation leading to the observed decrease in trabecular bone volume and BMD. These novel in vivo effects of TZDs on bone are of clinical relevance as patients with type 2 diabetes mellitus and other insulin resistant states treated with these agents may potentially be at increased risk of osteoporosis.

Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

2014 ◽  
Vol 84 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Hanan A. Alfawaz ◽  
Abdulrahman S. Al-Ajlan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Serum Selenium ◽  
Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women

IUBMB Life ◽  
2017 ◽  
Vol 69 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Nearmeen M. Rashad ◽  
Amal S. El-Shal ◽  
Rasha L. Etewa ◽  
Fady M. Wadea
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Lipocalin 2 ◽  
Obese Women ◽  
Early Predictors

scholarly journals Type 2 diabetes mellitus – IL-8 and IL-10 profile in patients with intraabdominal postoperative abscesses

2020 ◽  
Vol 73 (2) ◽  
pp. 220-223
Author(s):  
Valeriy V. Boyko ◽  
Artem S. Riga
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Nosocomial Infection ◽  
Perioperative Period ◽  
Serum Levels ◽  
Surgical Trauma ◽  
Abdominal Abscesses ◽  
Group 2

The aim: To assess of pro-inflammatory IL-8 and anti-inflammatory IL-10 serum concentration in patients with T2DM with intraabdominal postoperative abscesses in perioperative period. Materials and methods: The 48 participants, aged 40 – 75 years, among them 24 males and 24 females. All patients were divided into groups: group 1 – 12 patients with T2DM and intra-abdominal postoperative abscesses, group 2 – 12 patients without T2DM but with intra-abdominal postoperative abscesses and 24 healthy individuals. The level of IL-8and IL-10 serum was determined on the day before surgery, on the 2-3rd and 5-7th day after surgery in patients with type 2 diabetes and intra-abdominal postoperative abscesses. Results and conclusions: The trajectories of the level of interleukins in patients with type 2 Diabetes mellitus were different from the trajectories of their level in patients without diabetes, which indicates a special immune response to nosocomial infection and surgical trauma. The mechanism of changes in serum levels of IL-8 and IL-10 in patients with type 2 Diabetes mellitus and postoperative intra-abdominal abscesses should be further studied in future studies on the specific causative agent of nosocomial infection and the cytokine response to it.

scholarly journals Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengni Li ◽  
Rongping Fan ◽  
Xuemin Peng ◽  
Jiaojiao Huang ◽  
Huajie Zou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Serum Levels ◽  
Hs Crp ◽  
The Relationship

BackgroundPrevious studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear.AimTo Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status.MethodsA total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models.ResultsSerum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P &lt;0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P&lt;0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=&lt;0.001) but no significant correlation to HOMA-IR(respectively; P&gt;0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P&lt;0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P&lt;0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%.ConclusionThis study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

scholarly journals Levels of soluble cell adhesion molecules in type 2 diabetes mellitus patients with macrovascular complications

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989385
Author(s):  
Gehan A Hegazy ◽  
Zuhier Awan ◽  
Enayat Hashem ◽  
Nabil Al-Ama ◽  
Asmaa Basha Abunaji
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Serum Levels ◽  
Macrovascular Complications ◽  
Soluble Adhesion Molecules

Objective Type 2 diabetes mellitus (T2DM) is a main risk factor for development of cardiovascular diseases (CVDs) and endothelial dysfunction. This study aimed to investigate serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), and endothelium selectin (sE-selectin) in T2DM patients with macrovascular complications. Methods A cross-sectional study of 21 controls, 30 T2DM patients without CVDs, and 30 T2DM patients with CVDs was conducted. Serum levels of soluble adhesion molecules including sVCAM-1, sICAM-1, and sE-selectin were determined using ELISA. Results Serum levels of sVCAM-1, sICAM-1, and sE-selectin were higher in T2DM patients than in controls. Levels of serum sVCAM-1 were higher in T2DM patients with CVDs compared with T2DM patients without CVDs. In T2DM patients with CVDs, significant positive associations were observed between sVCAM-1, sICAM-1, and sE-selectin levels (r = 0.575, p = 0.001 and r = 0.378, p = 0.040). Conclusions Circulating levels of soluble adhesion molecules were elevated in T2DM patients, regardless of whether the patients had cardiovascular complications. Only sVCAM-1 was considered a useful marker for the prediction of CVDs in T2DM patients.

Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

2018 ◽  
Vol 46 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Zeeshan Ali ◽  
P. Charukeshi Chandrasekera ◽  
John J. Pippin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
Animal Research ◽  
Therapeutic Options ◽  
Research Findings

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human-based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

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