• Title/Summary/Keyword: Diabetes type I

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Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children

  • Maheshwari, Anshu;He, Zhaoping;Weidner, Melissa Nicole;Lin, Patrick;Bober, Ryan;Del Rosario, Fernando J.
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.24 no.2
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    • pp.218-229
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    • 2021
  • Purpose: Serological tests of tissue transglutaminase (TTG) and deamidated gliadin (DGP) antibodies for celiac disease diagnosis show conflicting correlation with histology in young children and in type 1 diabetes mellitus (T1DM). Tests' ability to predict histology and cutoff values based on age and T1DM was evaluated. Methods: A retrospective study of children who had celiac serological tests between 6/1/2002 and 12/31/2014 at a pediatric hospital. Results: TTG IgA displayed similar results in predicting histology between <4.0 and ≥4.0 years age groups with sensitivity 98% and 93%, and specificity 88% and 86%, respectively. In children <4.0 years old, sensitivity for DGP antibodies was 100% and specificity 94%; in ≥4.0 years age groups, sensitivity was 60%, 88% for DGP IgA and IgG and specificity 95%, 96%, respectively. TTG IgA had low specificity in patients with T1DM compared with non-T1DM, 42% vs. 91%. Positive TTG IgA with normal histology was associated with higher T1DM prevalence at 36% compared with negative tests at 4%. Finally, the TTG IgA cutoff value was higher in T1DM at 36 vs. 16.3 units in non-T1DM. DGP IgG cutoff showed similar values between age groups; TTG IgA and DGP IgA cutoffs were lower in <4.0 years at 8.3 and 11.9 units than ≥4.0 years at 23.4 and 19.9, respectively. Conclusion: TTG IgA is sufficient for the <4.0 years age group and DGP antibodies had no advantage over TTG IgA in older children. The cutoff value to determine a positive TTG IgA should be higher for children with T1DM.

Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations

  • So, Seongjun;Lee, Song;Lee, Yeonmi;Han, Jongsuk;Kang, Soonsuk;Choi, Jiwan;Kim, Bitnara;Kim, Deokhoon;Yoo, Hyun-Ju;Shim, In-Kyong;Oh, Ju-Yun;Lee, Yu-Na;Kim, Song-Cheol;Kang, Eunju
    • BMB Reports
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    • v.55 no.9
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    • pp.453-458
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    • 2022
  • Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

Effect of Taurine Supplement on the Lipid Peroxide Formation and the Activity of Glutathione-Dependent Enzyme in the Liver and Islet of Diabetic Model Mice (당뇨 모델쥐의 간관 췌장에서 타우린이 지질과산화물 생성과 글루타티온 의존성 효소의 활성에 미치는 영향)

  • 임은영;김해리
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.2
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    • pp.195-201
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    • 1995
  • In this study we wanted to investigate the effect of taurine supplement on the lipid peroxide formation and the activities of glutathione(GSH) dependent enzyme in diabetic model mice. We induce type I diabetes mellitus with alloxan injeciton in ICR mice and type II with high calorie diet in genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5%(w/v) for seven days. In type I diabetic model, the malondialdehyde(MDA) of liver and islet significantly increased compared to control group and they significantly decreased by taurine supplement. In type II diabetic model, the concentration of MDA was not changed by taurine supplement. The activities of GSH-peroxidase(GPX) of liver and islet increased in type I diabetic group while decreased in type II. GPX activities were not changed by taurine supplement in the liver of both types but increased in the islet of type II. Taurine supplement has no effect on the activities of GSH S-transferase(GST) in both types. From these results, we suggest that taurine supplement protect against lipid peroxide formation in diabetic model of type I.

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Inflammasomes: Molecular Regulation and Implications for Metabolic and Cognitive Diseases

  • Choi, Alexander J.S.;Ryter, Stefan W.
    • Molecules and Cells
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    • v.37 no.6
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    • pp.441-448
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    • 2014
  • Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model

  • Yeo, Hyeon Ji;Yeo, Eun Ji;Shin, Min Jea;Choi, Yeon Joo;Lee, Chi Hern;Kwon, Hyeok Yil;Kim, Dae Won;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.51 no.7
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    • pp.362-367
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    • 2018
  • A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic ${\beta}$-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F ${\beta}$-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic ${\beta}$-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of $NF-{\kappa}B$ and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice.

Risk factors of type 2 diabetes among Korean adults: The 2001 Korean national health and nutrition examination survey

  • Chung, Hae-Rang;Perez-Escamilla, Rafael
    • Nutrition Research and Practice
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    • v.3 no.4
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    • pp.286-294
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    • 2009
  • This study aimed to identify risk factors for type 2 diabetes (T2D) in Korea, a rapidly changing country. Data of 5,132 adults aged 20-85 were used from the 2001 Korean Health and Nutrition Examination Survey. Multiple logistic regression was carried out to identify risk factors for T2D. Three models were specified: (i) socioeconomic and demographic factors (model 1: age, gender, education, poverty income ratio, employment), (ii) behavioral risk factors and covariates (model 2: obesity, physical activity, smoking, alcohol drinking, dietary quality, family history of T2D, co-morbidity) and (iii) socioeconomic, demographic, and behavioral factors (model 3). The prevalence of T2D was 7.4%. Less education (OR 1.41, 95% CI 1.08-1.84), age (OR 2.19, 95% CI 1.56-3.08 in 40-59 yrs, OR 4.05, 95% CI 2.76-5.95 in 60 yrs + comparing to 20-39 yrs) and abdominal obesity (OR 2.24, 95% CI 1.79-2.82) were risk factors for T2D even after controlling for other factors simultaneously. There was a significant association of T2D with ever smoking (OR 1.34, 95% CI 1.06-1.67). The relationship of age with T2D was modified by gender in model 1 and the relationship of smoking with T2D was modified by obesity in model 2. Less educated, older, obese or ever smokers were more likely to have T2D. Gender mediated the relationship of age, and obesity mediated the relationship of smoking, with T2D. Intervention programs for T2D in Korea should take the interactions among risk factors into account.

In Silico Analysis of Potential Antidiabetic Phytochemicals from Matricaria chamomilla L. against PTP1B and Aldose Reductase for Type 2 Diabetes Mellitus and its Complications

  • Hariftyani, Arisvia Sukma;Kurniawati, Lady Aqnes;Khaerunnisa, Siti;Veterini, Anna Surgean;Setiawati, Yuani;Awaluddin, Rizki
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.99-114
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    • 2021
  • Type 2 diabetes mellitus (T2DM) and its complications are important noncommunicable diseases with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase inhibitors are recently approached and advanced for T2DM and its complications therapy. Matricaria chamomilla L. is acknowledged as a worldwide medicinal herb that has many beneficial health effects as well as antidiabetic effects. Our research was designed to determine the most potential antidiabetic phytochemicals from M. chamomilla employing in silico study. 142 phytochemicals were obtained from the databases. The first screening employed iGEMdock and Swiss ADME, involving 93 phytochemicals. Finally, 30 best phytochemicals were docked. Molecular docking and visualization analysis were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. Molecular docking results demonstrate that ligand-protein interaction's binding affinities were -5.16 to -7.54 kcal/mol and -5.30 to -12.10 kcal/mol for PTP1B and aldose reductase protein targets respectively. In silico results demonstrate that M. chamomilla has potential antidiabetic phytochemical compounds for T2DM and its complications. We recommended anthecotulide, quercetin, chlorogenic acid, luteolin, and catechin as antidiabetic agents due to their binding affinities against both PTP1B and aldose reductase protein. Those phytochemicals' significant efficacy and potential as antidiabetic must be investigated in further advanced research.

Effect of the Deep Sea Water on the Blood Glucose and the Langerhans' Islet in the STZ-induced type I Diabetic Mice (해양심층수 섭취가 STZ로 유발된 제 1형 당뇨 생쥐의 혈당치 및 췌도에 미치는 영향)

  • Jung, Jae-Bong;Jung, Ji-Yoon;Yoon, Myung-Hee
    • Journal of Life Science
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    • v.19 no.7
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    • pp.923-927
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    • 2009
  • Effects of deep sea water on blood glucose and the Langerhans' islet in STZ-induced type I diabetic mice were investigated. Results showed that diabetic symptoms in STZ-induced diabetic mice improve with a supplement of deep sea water. That is, the level of blood glucose was lower, the area of the Langerhan' islet was wider, and the number of pancreatic $\beta$-cells was larger in the diabetic mice supplied with deep sea water than in the diabetic mice supplied with tap water. Such effects might be related to the high level of Mg$^{2+}$ in the deep sea water.

Trends in the Studies of Glucose-Responsive Drug Delivery Systems (포도당 응답성 약물전달시스템의 연구 동향)

  • Jo, Seong-Min;Kim, Jin-Chul
    • Applied Chemistry for Engineering
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    • v.20 no.6
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    • pp.581-585
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    • 2009
  • Diabetes is caused by the lack of insulin secretion or the reduction in its sensitivity. The recent treatments for diabetes do not fulfill the requirements for the maintaining of normal blood glucose level. The most frequently used treatment for type I diabetes is an insulin injection. However, the insulin injection often involves the life-threatening risk and the low compliance of patients. Accordingly, extensive studies have been done to overcome the shortcomings of the injection. A representative approach is to employ self-regulated insulin delivery systems. This report includes the principles of glucose-responsive release in the self-regulated insulin delivery systems.