• Title/Summary/Keyword: Diabetes type I

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Cellular and Molecular Roles of $\beta$ Cell Autoantigens, Macrophages and T Cells in the Pathogenesis of Automimmune Diabetes

  • Yoon, Ji-Won;Jun, Hee-Sook
    • Archives of Pharmacal Research
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    • v.22 no.5
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    • pp.437-447
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    • 1999
  • Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

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The Association Between PM2.5 Exposure and Diabetes Mellitus Among Thai Army Personnel

  • Apisorn Laorattapong;Sarun Poobunjirdkul;Thanapoom Rattananupong;Wiroj Jiamjarasrangsi
    • Journal of Preventive Medicine and Public Health
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    • v.56 no.5
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    • pp.449-457
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    • 2023
  • Objectives: This study investigated the association between baseline exposures to particulate matter with a diameter <2.5 microns (PM2.5) and subsequent temporal changes in PM2.5 exposure with the incidence of type 2 diabetes among Royal Thai Army personnel. Methods: A retrospective cohort study was conducted using nationwide health check-up data from 21 325 Thai Army personnel between 2018 and 2021. Multilevel mixed-effects parametric survival statistics were utilized to analyze the relationship between baseline (i.e., PM2.5-baseline) and subsequent changes (i.e., PM2.5-change) in PM2.5 exposure and the occurrence of type 2 diabetes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were employed to assess this association while considering covariates. Results: There was a significant association between both PM2.5 baseline and PM2.5-change and the incidence of type 2 diabetes in a dose-response manner. Compared to quartile 1, the HRs for quartiles 2 to 4 of PM2.5-baseline were 1.11 (95% CI, 0.74 to 1.65), 1.51 (95% CI, 1.00 to 2.28), and 1.77 (95% CI, 1.07 to 2.93), respectively. Similarly, the HRs for quartiles 2 to 4 of PM2.5-change were 1.41 (95% CI, 1.14 to 1.75), 1.43 (95% CI, 1.13 to 1.81) and 2.40 (95% CI, 1.84 to 3.14), respectively. Conclusions: Our findings contribute to existing evidence regarding the association between short-term and long-term exposure to PM2.5 and the incidence of diabetes among personnel in the Royal Thai Army.

Metabolite analysis in the type 1 diabetic mouse model

  • Park, Sung Jean
    • Journal of the Korean Magnetic Resonance Society
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    • v.25 no.3
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    • pp.33-38
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    • 2021
  • Type 1 diabetes mellitus (T1DM) is caused by insufficient production of insulin, which is involved in carbohydrate metabolism. Type 2 diabetes mellitus (T2DM) has insulin resistance in which cells do not respond adequately to insulin. The purpose of this study was to estimate the characteristics of type 1 diabetes using streptozotocin-treated mice (STZ-mouse). The sera samples were collected from the models of hyperglycemic mouse and healthy mouse. Based on the pair-wise comparison, five metabolites were found to be noticeable: glucose, malonic acid, 3-hyroxybutyrate, methanol, and tryptophan. It was very natural glucose was upregulated in STZ-mouse. 3-hyroxybutyrate was also increased in the model. However, malonic acid, tryptophan, and methanol was downregulated in STZ-mouse. Several metabolites acetoacetate, acetone, alanine, arginine, asparagine, histidine, lysine, malate, methionine, ornithine, proline, propylene glycol, threonine, tyrosine, and urea tended to be varied in STZ-mouse while the statistical significance was not stratified for the variation. The multivariate model of PCA clearly showed the group separation between healthy control and STZ-mouse. The most significant metabolites that contributed the group separation included glucose, citrate, ascorbate, and lactate. Lactate did not show the statistical significance of change in t-test while it tends to down-regulated both in DNP and Diabetes.

Current Status of Stem Cell Treatment for Type I Diabetes Mellitus

  • Kakkar, Anupama;Sorout, Ashima;Tiwari, Mahak;Shrivastava, Pallavi;Meena, Poonam;Kumar Saraswat, Sumit;Srivastava, Supriya;Datt, Rajan;Pandey, Siddharth
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.699-709
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    • 2018
  • BACKGROUND: Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans. METHODS: Current treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into ${\beta}$ islet cells. RESULTS: These stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms. CONCLUSION: Stem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.

Prediction of Type 2 Diabetes Remission after Bariatric or Metabolic Surgery

  • Park, Ji Yeon
    • Journal of Obesity & Metabolic Syndrome
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    • v.27 no.4
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    • pp.213-222
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    • 2018
  • Bariatric surgery has evolved from a surgical measure for treating morbid obesity to an epochal remedy for treating metabolic syndrome as a whole, which is represented by type 2 diabetes mellitus. Numerous clinical trials have advocated bariatric or metabolic surgery over nonsurgical interventions because of markedly superior metabolic outcomes in morbidly obese patients who satisfy traditional criteria for bariatric surgery (body mass index [BMI] >$35kg/m^2$) and in less obese or simply overweight patients. Nevertheless, not all diabetes patients achieve the most desirable outcomes; i.e., diabetes remission after metabolic surgery. Thus, candidates for metabolic surgery should be carefully selected based on comprehensive preoperative assessments of the risk-benefit ratio. Predictors for diabetes remission after metabolic surgery may be classified into two groups based on mechanism of action. The first is indices for preserved pancreatic beta-cell function, including younger age, shorter duration of diabetes, and higher C-peptide level. The second is the potential for an insulin resistance reduction, including higher baseline BMI and visceral fat area. Several prediction models for diabetes remission have been suggested by merging these two to guide the joint decision-making process between clinicians and patients. Three such models, DiaRem, ABCD, and individualized metabolic surgery scores, provide an intuitive scoring system and have been validated in an independent external cohort and can be utilized in routine clinical practice. These prediction models need further validation in various ethnicities to ensure universal applicability.

The Effects of Diet Education Contents for the Customized Serious Game Development in Type II Diabetes (제2형 당뇨환자 기능성게임 개발을 위한 식이교육 콘텐츠 효과)

  • Kim, Yu-Jeong
    • Journal of Korea Game Society
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    • v.16 no.4
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    • pp.87-96
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    • 2016
  • This study was carried out to investigate the effects of contents for the serious game development of the customized diet education in Type II Diabetes. Because the development of the existing serious game focuses on Type I Diabetes, this study was designed to carry out customized education through the interaction between Type II Diabetes and health manager. The period of data collection was from July 11 to December 26 in Y2015, the subjects were selected from a total of 26 people suitable for Type II diabetes who visited the public health center to apply for a diabetic diet education and completed the 8 continued education. After receiving customized diet prototype education, the self-care behaviors and HbA1C of the subjects were statistically significantly increased(p<.05)

Compensation of Variation from Long-Term Spectral Measurement for Non-invasive Blood Glucose in Mouse by Near-Infrared Spectroscopy (근적외분광분석법을 이용한 생쥐꼬리에서의 비침습 혈당 정량시 장기간 측정에 따른 변이 요인의 보정)

  • 백주현;강나루;우영아;김효진
    • YAKHAK HOEJI
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    • v.48 no.3
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    • pp.177-181
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    • 2004
  • Non-invasive blood glucose measurement from mouse tail was performed by near-infrared (NIR) spectroscopy. Three groups; normal, type I diabetes (insulin dependent diabetes mellitus, IDDM), type II diabetes (non-insulin dependent diabetes mellitus, NIDDM) group, were studied over a 10 weeks period with the collection of near-infrared (NIR) spectra. Spectral variations from long-term measurement (10 weeks) from dramatic and nonlinear changes in the optical properties of the live tissue sample were compensated by chemometrics techniques such as principle component analysis (PCA) and partial least squares (PLS) regression. The effect from mouse body temperature changes on NIR spectral data was also considered. This study showed that the compensation of variations from long-term measurement and temperature changes improved calibration accuracy of non-invasive blood glucose measurement.

Effect of Non-sterilized Makgeolli Consumption on Blood Glucose Level and Survival Rate in Streptozotocin-induced Type I Diabetic Mice (Streptozotocin으로 유도된 제1형 당뇨 생쥐에서 생막걸리 투여가 혈당 및 생존률에 미치는 영향)

  • Lee, Hyun Sook;Kim, Soon Mi
    • Journal of the Korean Society of Food Culture
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    • v.30 no.6
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    • pp.818-824
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    • 2015
  • Makgeolli is a health beneficial food for diabetes compared to other alcoholic beverages. We examined the effect of Makgeolli on blood glucose level and survival rate in a streptozotocin (STZ)-induced diabetic mouse model. We force fed 30 male STZ-induced diabetic ICR mice Makgeolli consisting of 6% alcohol (DM-MAK), 6% ethanol (DM-EtOH), or distilled water (DM-DW) for 4 weeks. In the DM-MAK group, food intake and water intake were higher than those of other groups after 4 weeks. Body weight, however, was not different among the experimental groups. We also found no significant difference in blood glucose level among the experimental groups. In normal ICR mice fed Makgeolli for 1 week, the area of the blood glucose curve was higher than those of other groups fed 6% ethanol, 2% glucose, or distilled water. Survival rates of STZ-induced diabetic mice fed Makgeolli, 6% ethanol, or DW for 4 weeks were 100%, 25%, and 62.5%, respectively. In conclusion, Makgeolli had no beneficial effect on blood glucose in a STZ-induced diabetic mouse model, although their survival rate was high. These results show that Makgeolli has an effect on type 1 diabetes through other mechanisms than blood glucose control.

Effects of Samguiyong-tang on the Blood Glucose Levels in Normal Rats or Diabetic Rats Induced by Streptozotocin (삼귀용탕(蔘歸茸湯)이 정상 흰쥐 및 Streptozotocin으로 유도된 당뇨병 흰쥐의 혈당에 대한 영향)

  • Kim, Hyeung-Cheol;Han, Hyo-Sang;Lee, Young-Jong
    • The Korea Journal of Herbology
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    • v.24 no.4
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    • pp.25-30
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    • 2009
  • Objectives : In order to evaluate the effect of Samguiyong-tang (SGYT) on diabetes, we prepared two types of Samguiyong-tang (Type-I and -II) which was composed of three kinds of oriental drug such as Ginseng, Angelica gigantis radix and Deer antler. Type I was traditional hot-water extract prepared from three kinds of drug, and Type II was the mixture of ethanol-extract of ginseng and hot-water extract prepared from the other two drugs. Methods : We tested the effects of SGYT on the blood glucose levels in normal rats by the method of glucose tolerance test. And also examined the effects of SGYT on the levels in normal rats or diabetic rats induced by Streptozotocin during 20 days. Results : 1. In the course of oral glucose tolerance test, the blood glucose level decreased by administration of SGYT I or II in normal rats. 2. In the course administration of SGYT during 20 days in normal rats, the blood glucose levels decreased until day 4 by Type I or Type II, but thereafter the level was recovered to the normal. 3. In the course administration of SGYT during 20 days in the diabetic rats induced by streptozotocin, Type I (SGYT) had some effect on the blood glucose levels only at 12 day, and Type II (SGYT) decreased the levels from 6th day and so on, significantly. Conclusions : The results suggested that SGYT II had some decreasing effects on the blood glucose levels in diabetic rats induced by Streptozotocin.

Identification of Genetic Variations in CBL, SORBS1, CRK, and RHOQ, Key Modulators in the CAP/TC10 Pathway of Insulin Signal Transduction, and Their Association with Type 2 Diabetes Mellitus in the Korean Population

  • Hong, Kyung-Won;Jin, Hyun-Seok;Lim, Ji-Eun;Go, Min-Jin;Lee, Jong-Young;Hwang, Sue-Yun;Park, Hun-Kuk;Oh, Berm-Seok
    • Genomics & Informatics
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    • v.7 no.2
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    • pp.53-56
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    • 2009
  • Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.