scholarly journals Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2 Diabetes

2014 ◽  
Vol 83 (2) ◽  
pp. 792-801 ◽  
Author(s):  
Bruno S. Herrera ◽  
Hatice Hasturk ◽  
Alpdogan Kantarci ◽  
Marcelo O. Freire ◽  
Olivia Nguyen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Transgenic Animals ◽  
Genetically Engineered ◽  
Mitogen Activated Protein Kinase ◽  
Air Pouch ◽  
Content Type ◽  
Genetically Engineered Mice ◽  
The Impact

Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain ofdb/ERV1mice, were used to determine the impact of RvE1 on the phagocytosis ofPorphyromonas gingivalisin T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeledP. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate thein vivoimpact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis ofP. gingivalisin WT animals but had no impact indb/dbanimals. InERV1-transgenic andERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals.In vivodorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis ofP. gingivalisin the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressingERV1.

Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: merging bioinformatics with in vivo analysis

2021 ◽  
pp. 112325
Author(s):  
Katarina Baralić ◽  
Katarina Živančević ◽  
Dragica Jorgovanović ◽  
Dragana Javorac ◽  
Jelena Radovanović ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Bisphenol A ◽  
In Vivo Analysis ◽  
The Impact

scholarly journals Islet macrophages drive islet vascular remodeling and compensatory hyperinsulinemia in the early stages of diabetes

2019 ◽  
Author(s):  
Manesh Chittezhath ◽  
Divya Gunaseelan ◽  
Xiaofeng Zheng ◽  
Riasat Hasan ◽  
Vanessa SY Tay ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Vascular Remodeling ◽  
Ex Vivo ◽  
Vascular Density ◽  
Rapid Progression ◽  
List Type ◽  
The Impact

Abstractβ-cells respond to peripheral insulin resistance by increasing circulating insulin in early type-2 diabetes (T2D). Islet remodeling supports this compensation but the drivers of this process remain poorly understood. Infiltrating macrophages have been implicated in late stage T2D but relatively little is known on islet resident macrophages, especially in early T2D. We hypothesize that islet resident macrophages contribute to islet vascular remodeling and hyperinsulinemia, the failure of which results in a rapid progression to T2D. Using genetic and diet-induced models of compensatory hyperinsulinemia we show that its depletion significantly compromises islet remodeling in terms of size, vascular density and insulin secretion capacity. Depletion of islet macrophages reduces VEGF-A secretion from both human and mouse islets ex vivo and the impact of reduced VEGF-A functionally translates to delayed re-vascularization upon transplantation in vivo. Hence, we show a new role of islet resident macrophages in the context of early T2D and suggest that there is considerable utility in harnessing islet macrophages to promote islet remodeling and islet insulin secretion capacity.HighlightsThe compensatory hyperinsulinemic phase of type-2 diabetes is accompanied with significant pancreatic islet remodeling.Bona fide islet resident macrophages are increased during the diabetic compensation phase by largely in situ proliferation.Ablating macrophages severely compromises the islet remodeling process and exacerbates glycemic control in vivo.Mouse and human islet macrophages contribute VEGF-A to the islet environment.Specific removal of islet macrophages delays islet vascularization in compensatory hyperinsulinemic mice.

Gene Expression Analysis of Troglitazone Reveals Its Impact on Multiple Pathways in Cell Culture: A Case for In Vitro Platforms Combined with Gene Expression Analysis for Early (Idiosyncratic) Toxicity Screening

2006 ◽  
Vol 25 (2) ◽  
pp. 85-94 ◽  
Author(s):  
Gordon Vansant ◽  
Patrick Pezzoli ◽  
Robert Saiz ◽  
Aaron Birch ◽  
Chris Duffy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Peroxisome Proliferator ◽  
Toxicity Screening ◽  
The Impact

Peroxisome proliferator-activated receptor gamma (PPAR γ) agonists of the thiazolidinedione family are used for the treatment of type 2 diabetes mellitus due to their ability to reduce glucose and lipid levels in patients with this disease. Three thiazolidinediones that were approved for treatment are Rezulin (troglitazone), Avandia (rosiglitazone), and Actos (pioglitazone). Troglitazone was withdrawn from the market due to idiosyncratic drug toxicity. Rosiglitazone and pioglitazone are still on the market for the treatment of type 2 diabetes. The authors present data from a gene expression screen that compares the impact these three compounds have in rats, in rat hepatocytes, and in the clone 9 rat liver cell line. The authors monitored the changes in expression in multiple genes, including those related to xenobiotic metabolism, proliferation, DNA damage, oxidative stress, apoptosis, and inflammation. Compared to the other two compounds, troglitazone had a significant impact on many of the pathways monitored in vitro although no major perturbation was detected in vivo. The changes detected predict not only general toxicity but potential mechanisms of toxicity. Based on gene expression analysis, the authors propose there is not just one but multiple ways troglitazone could be toxic, depending on a patient’s environment and genetic makeup, including immune response-related toxicity.

scholarly journals The Impact of Altered Metabolism on the Regulation of IGF-II/H19 Imprinting Status in Prostate Cancer.

2020 ◽  
Author(s):  
Georgina Kingshott ◽  
Kalina Biernacka ◽  
Alex Sewell ◽  
Paida Gwiti ◽  
Rachel Barker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Small Subset ◽  
Cancer Type ◽  
Tissue Samples ◽  
Positive Correlation ◽  
The Impact

Abstract Background: Prostate cancer is the most frequently diagnosed cancer type and the second major cause of cancer deaths amongst men. A link exists between obesity, type 2 diabetes, and cancer risk. Insulin-like growth factor II (IGF-II) plays a role in numerous cellular events, including proliferation and survival. The IGF-II gene shares its locus with the lncRNA, H19. IGF-II/H19 was also the first gene to be identified as being ‘imprinted’ – where the paternal copy is not transcribed. This silencing phenomenon is lost in many cancer types. Methods: We disrupted imprinting behaviour in vitro through the alteration of metabolic conditions and quantified it using RFLP, qPCR and pyrosequencing; changes to peptide were measured using RIA. Prostate tissue samples were analysed using ddPCR, pyrosequencing and IHC. We then compared with in silico data, provided by TGCA on the cBIO Portal.Results: Disruption of imprinting behaviour, in vitro, occurs at the molecular level with no changes to peptide. In vivo, most specimens primarily retained imprinting status, apart from a small subset which showed reduced imprinting. A positive correlation was seen between IGF-II and H19 mRNA expression, which concurred with findings of larger Cancer Genome Atlas (TGCA) cohorts. This positive correlation did not affect IGF-II peptide. Conclusions: Type 2 diabetes and / or obesity directly affect regulation growth factors involved in carcinogenesis.Trial registration: Prostate Cancer Evidence of Exercise and Nutrition Trial: nutritional and physical activity interventions for men with localised prostate cancer – feasibility study (ISRCTN99048944). Registered on 17 November 2014

The Impact of Obesity on Incidence of Type 2 Diabetes Mellitus (T2DM) among Women with Polycystic Ovary Syndrome (PCOS)

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1612-P
Author(s):  
NADIRA SULTANA KAKOLY ◽  
ARUL EARNEST ◽  
HELENA TEEDE ◽  
LISA MORAN ◽  
DEBORAH LOXTON ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
The Impact

Model estimates of the results of diabetes patients using modern glucometers with tri-color technology for displaying test results

2019 ◽  
pp. 81-89
Author(s):  
Larisa Dmitrievna Popovich ◽  
Svetlana Valentinovna Svetlichnaya ◽  
Aleksandr Alekseevich Moiseev
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Economic Benefits ◽  
Test Results ◽  
Self Monitoring ◽  
Patients With Diabetes ◽  
The Impact

Diabetes – a disease in which the effect of the treatment substantially depends on the patient. Known a study showed that the use of glucometers with the technology of three-color display of test results facilitates self-monitoring of blood sugar and leads to a decrease in glycated hemoglobin (HbAlc). Purpose of the study: to modeling the impact of using of a glucometer with a color-coded display on the clinical outcomes of diabetes mellitus and calculating, the potential economic benefits of reducing the hospitalization rate of patients with diabetes. Material and methods. Based on data from two studies (O. Schnell et al. and M. Baxter et al.) simulation of the reduction in the number of complications with the use of a glucometer with a color indication. In a study by O. Schnell et al. a decrease of HbA1c by 0.69 percent is shown when using the considered type of glucometers, which was the basis of the model. Results. In the model, the use of a glucometer with a color-coded display for type 1 diabetes led to a decrease in the total number of complications by 9.2 thousand over 5 years per a cohort of 40 thousand patients with different initial levels of HbA1c. In a cohort of 40 thousand patients with type 2 diabetes, the simulated number of prevented complications was 1.7 thousand over 5 years. When extrapolating these data to all patients with diabetes included in the federal register of diabetes mellitus (FRD), the number of prevented complications was 55.4 thousand cases for type 1 diabetes and 67.1 thousand cases for type 2 diabetes. The possible economic effect from the use of the device by all patients with a diagnosis of diabetes, which are included in the FRD, estimated at 1.5 billion rubles for a cohort of patients with type 1 diabetes and 5.3 billion rubles for patients with type 2 diabetes. Conclusion. Improving the effectiveness of self-monitoring, which is the result of the use of glucometers with color indicators, can potentially significantly reduce the incidence of complications in diabetes and thereby provide significant economic benefits to society.

The Impact of Bariatric Surgery in Patients with Type-2 Diabetes Mellitus

2011 ◽  
Vol 7 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Richdeep S. Gill ◽  
Arya M. Sharma ◽  
David P. Al-Adra ◽  
Daniel W. Birch ◽  
Shahzeer Karmali
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Type 2 Diabetes Mellitus ◽  
The Impact

scholarly journals Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

2021 ◽  
Vol 9 (1) ◽  
pp. e001413
Author(s):  
Jonathan Yap ◽  
Kamalesh Anbalakan ◽  
Wan Ting Tay ◽  
Daniel Ting ◽  
Carol Yim Cheung ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glycemic Control ◽  
Microvascular Complications ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Microvascular Complication ◽  
The Impact ◽  
Hba1c Levels

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.

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