Protective effects of combined micronutrients on islet β-cells of streptozotocin-induced diabetic mice

2009 ◽  
Vol 79 (2) ◽  
pp. 104-116 ◽  
Author(s):  
Ying Chang ◽  
Gui-Zhen Zhang ◽  
Song-Lan Piao ◽  
Shen Gao ◽  
De-Ming Zheng ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Molecular Mechanisms ◽  
Interleukin 10 ◽  
Protective Effects ◽  
Diabetic Mice ◽  
T Helper ◽  
T Helper 1 ◽  
Β Cells ◽  
High Blood Glucose ◽  
Glucose Levels

There is a tendency for the incidence of diabetes in a population to increase with an improvement in living standards. This would imply the involvement of nutritional factors in the development of diabetes, and so nutritional considerations could be a key aspect in the research and development of an effective remedy for diabetes. In this study, combined micronutrients (selenium, vitamin E, vanadium, and chromium) were orally supplemented to streptozotocin-induced diabetic mice. Results showed that combined micronutrients could decrease the high blood glucose levels (p<0.05 or p<0.01) of diabetic mice. The protective effects of combined micronutrients on structures of β-cells in pancreatic islets of diabetic mice were observed histopathologically and ultrastructurally. In addition, the supplementation of combined micronutrients increased insulin expression by β-cells in pancreatic islets of diabetic mice at both translational and transcriptional levels. The immune molecular mechanisms involved were preliminarily regarded as downregulation of the expression of pathogenic T-helper 1 lymphocyte (Th1) cytokine tumor necrosis factor-α (TNF-α) (p<0.01) along with upregulation of the expression of protective T-helper 2 lymphocyte Th2 cytokine interleukin 10 (IL-10) (p<0.01) which ameliorates the Th1/Th2 imbalance in diabetes. In conclusion, supplementation of combined micronutrients to diabetic mice could effectively improve disordered glucose metabolism, protect islet structures, and improve the function of β-cells in pancreatic islets, which are affected by differential regulation of the expression of Th1/Th2 cytokines involved in the pathogenesis of diabetes.

scholarly journals Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1408 ◽  
Author(s):  
Catalina Prieto ◽  
Bárbara Casas ◽  
Paulina Falcón ◽  
Andrea Villanueva ◽  
Pablo Lois ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Trophic Factors ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Placental Angiogenesis

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.

scholarly journals C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis

2016 ◽  
Vol 231 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Mahendra Prasad Bhatt ◽  
Yeon-Ju Lee ◽  
Se-Hui Jung ◽  
Yong Ho Kim ◽  
Jong Yun Hwang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Damage ◽  
Protective Effects ◽  
Diabetic Mice ◽  
C Peptide ◽  
Glucose Levels

C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO− and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66shc after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO− in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage.

scholarly journals T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Mauricio Llaguno ◽  
Marcos Vinicius da Silva ◽  
Lara Rocha Batista ◽  
Djalma Alexandre Alves da Silva ◽  
Rodrigo Cunha de Sousa ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Chronic Phase ◽  
Interleukin 10 ◽  
T Helper ◽  
T Helper 1 ◽  
Cardiac Damage ◽  
Disease Treatment ◽  
Indeterminate Form ◽  
Ifn Γ

ABSTRACT The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25− and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.

A Commitment to Lineage

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-22-SCI-22
Author(s):  
Laurie H. Glimcher ◽  
Vanja Lazarevic ◽  
Joerg Ermann ◽  
Wendy Garrett
Keyword(s):  
Colorectal Cancer ◽  
Immune System ◽  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Inflammatory Diseases ◽  
Rectal Adenocarcinoma ◽  
Adaptive Immune System ◽  
T Helper ◽  
T Helper 1

Abstract Abstract SCI-22 The transcription factor T-bet, isolated in our laboratory a decade ago, is a master regulator of Type 1 immunity in cells of both the adaptive and innate immune system. In adaptive immunity, T-bet instigates genetic programs in T helper 1 (Th1) cells and is required for production of the hallmark Th1 cytokine IFNg. It simultaneously represses the differentiation of T helper 2 cells and the profibrotic cytokines IL-13 and TGFb. We have recently determined that T-bet is also a repressor of the Th17 genetic program and have established the molecular mechanisms that underpin that function. T-bet also controls the optimal differentiation and function of the cytolytic CD8 cell, and is required for the development of the natural killer T cell. T-bet deficient animals are largely protected from autoimmune/inflammatory diseases such as multiple sclerosis, systemic lupus, type 1 diabetes and inflammatory arthritis, but are susceptible to type 2 driven diseases such as asthma and scleroderma. An exception to this overall rule is our recent discovery that in the absence of an adaptive immune system, the majority of mice lacking T-bet develop a spontaneous ulcerative colitis that progresses to colonic dysplasia and rectal adenocarcinoma. This colitis and inflammation associated colorectal cancer are MyD88 independent, driven by colitogenic flora and ameliorated by treatment with TNF blockade, antibiotics, and transfer of T regulatory cells. This phenotype maps to the T-bet deficient dendritic cell that drives this pro-inflammatory program; selective over-expression of T-bet in DCs was sufficient to reduce colonic inflammation and prevent the progression to neoplasia. The molecular pathogenesis of TRUC colitis and colitis-associated colorectal (caCRC) shares several key features with human caCRC. This model of colitis and colitis-associated colorectal cancer provides opportunities to further understand host-microbial relationships in inflammation and neoplasia and test preventative and therapeutic strategies pre-clinically. The function and mechanism of action of T-bet in the pathogenesis of immune system driven diseases will be discussed. Disclosures: Glimcher: Merck: Consultancy, Patents & Royalties, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

scholarly journals Vitamin D and immunomodulation in the skin: a useful affirmative nexus

2021 ◽  
Author(s):  
Saptadip Samanta
Keyword(s):  
Vitamin D ◽  
Skin Diseases ◽  
Cell Formation ◽  
Interleukin 10 ◽  
The Body ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 17 ◽  
Vitamin D Receptors ◽  
T Helper 17 Cell

Skin is the largest organ of the body having multifunctional activities. It has a dynamic cellular network with unique immunologic properties to maintain defensive actions, photoprotection, immune response, inflammation, tolerogenic capacity, wound healing, etc. The immune cells of the skin exhibit distinct properties. They can synthesize active vitamin D [1,24(OH)2D3] and express vitamin D receptors. Any difficulties in the cutaneous immune system cause skin diseases (psoriasis, vitiligo, atopic dermatitis, skin carcinoma, and others). Vitamin D is an essential factor, exhibits immunomodulatory effects by regulating dendritic cells’ maturation, lymphocytes’ functions, and cytokine production. More specifically, vitamin D acts as an immune balancing agent, inhibits the exaggeration of immunostimulation. This vitamin suppresses T-helper 1 and T-helper 17 cell formation decreases inflammatory cytokines release and promotes the maturation of regulatory T cells and interleukin 10 secretion. The deficiency of this vitamin promotes the occurrence of immunoreactive disorders. Administration of vitamin D or its analogs is the therapeutic choice for the treatment of several skin diseases.

scholarly journals Amelioration of Hyperglycemia-Induced Nephropathy by 3,3′-Diindolylmethane in Diabetic Mice

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4474
Author(s):  
Kyeong-Mi Choi ◽  
Hwan-Soo Yoo
Keyword(s):  
Diabetic Nephropathy ◽  
Major Complication ◽  
Insulin Dependent Diabetes ◽  
Diabetic Mice ◽  
Renal Hypertrophy ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Dependent ◽  
Tgf Β1

Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. Diabetic nephropathy is a major complication of hyperglycemia. 3,3′-diindolylmethane (DIM)-a natural compound produced from indole-3-carbinol, found in cruciferous vegetables-enhances glucose uptake by increasing the activation of the insulin signaling pathway in 3T3-L1 adipocytes. In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. In mice, STZ induced hyperglycemia, hunger, thirst, and abnormally increased kidney weight and serum creatinine, which is a renal functional parameter. DIM decreased STZ-increased high blood glucose levels and food and water intake in diabetic mice. DIM also improved diabetic nephropathy by inhibiting the expression of PKC-α, the marker of albuminuria, and TGF-β1, an indicator of renal hypertrophy, in diabetic mice. Our findings suggest that DIM may ameliorate hyperglycemia and diabetic nephropathy through the inhibition of PKC-α and TGF-β1 signaling.

High Throughput Study for Molecular Mechanism of Metformin PreDiabetic Protection via Microarray Approach

2021 ◽  
Vol 21 ◽  
Author(s):  
Asma Y. Alrawashdeh ◽  
Mohammad A. AL Shhab ◽  
Malek A. Zihlif
Keyword(s):  
Blood Glucose ◽  
Test Group ◽  
Diabetic Rats ◽  
P Value ◽  
Protective Effects ◽  
Β Cells ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Before And After ◽  
Male Wistar Rats

Background:: Metformin is a biguanide that exhibits an antidiabetic, anticarcinogenic and anti-inflammatory properties. Despite well-known pancreatic protective effects, metformin's influence on pancreatic islet β-cell is yet considerably unknown. Protecting the functional insulin-producing β-cells in the pancreas is a key therapeutic challenge in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Objective:: Current study aimed to analyze the protective effects of metformin on streptozocin-induced diabetic rats in T1DM in hepatic tissues. Methods: : In the present study, male wistar rats (n=24) were randomly assigned into 2 groups (n=12 for each control and test) by which metformin (100 mg/kg/day) were given for 7 weeks. Afterwards, diabetes was induced by streptozocin (STZ) at a single dose of (150 mg/kg). Blood glucose was daily examined before and after STZ induction. The animals were euthanized by cervical dislocation 5 days after streptozocin injection, after which liver and pancreas were harvested from each rat. Results: : The biochemical analyses revealed that metformin resulted in significantly reduced plasma glucose levels and higher pancreatic insulin levels in the test group. Using a restrictive cut-off of at least 2-FC and an adjusted p-value (qvalue) of ≤0.05 a sum of 747 genes for the metformin group were shown to be differentially regulated compared to controls (320 Down and 427 Up), by which they were obtained from the liver. Furthermore, evidence is attained that metformin may hinder the loss of critical β-cells by reducing inflammatory and apoptosis signaling, promoting fatty acid β-oxidation and inducing metabolism. Conclusion: : Collectively, this study has demonstrated a decrease in blood glucose levels and a rise in insulin-levels and thus a consequent prophylactic effects in metformin-given STZ-induced diabetic rats.

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