• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권2호
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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.

• BMB Reports
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• 제55권9호
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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.

• 한국식품영양과학회지
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• 제24권2호
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• pp.195-201
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• 1995

당뇨 모델에서 타우린의 보강에 의한 지질과산화물의 생성과 GSH 관련 효소들의 활성에 미치는 영향을 알아보고자 alioxan을 이용한 I형과 KK-mouse에 고열량식이를 이용하여 II형 당뇨를 유도하였다. I형과 II형 각각에 정상대조군, 타우린보강군, 당뇨군, 타우린보강 당뇨군을 두어, 모두 8개 군으로 나누었으며, 타우린의 보강은 7일 동안 5%(w/v) 수준으로 자유로이 마시게 하였다. 간과 췌장에서 malondialdehycel(MDA), gluta-thione peroxidase(GPX), glutathions S-transferase(GST)의 활성을 측정하였다. 간조직에서 지질과산화물의 함량은 I형의 경우 당뇨군에서 매우 증가했고 타우린 보강에 의한 유의적으로 감소한 것을 볼 수 있었으며, II형에서는 타우린보강에 의해 유의적인 차이가 없었다. 췌장도 간과 같은 결과를 나타내었다. GPX의 활성은 간에서 I형 당뇨군이 유의적으로 증가했으나, II형 당뇨군에서는 유의적으로 감소했다. 타우린의 보강에 의해 GPX활성에는 유의적인 차이가 없었으며 췌장에서도 간과 비슷한 결과를 보였다. GST의 경우에도 당뇨 유도에 의한 활성 변화는 있었으나 타우린의 보강에 의한 활성 변화는 보이지 않았다. 이상의 결과들로 미루어 당뇨에 있어 타우린의 항산화작용은 당뇨 모델의 종류에 따라 다르며, GSH 관련 효소들의 활성변화 보다는 I형 당뇨 모델의 간과 췌장에서 지질과산화물의 생성을 억제하는 작용을 하리라고 생각 된다.

• Molecules and Cells
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• 제37권6호
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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.

• BMB Reports
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• 제51권7호
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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.

• Nutrition Research and Practice
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• 제3권4호
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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.

• Natural Product Sciences
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• 제27권2호
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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.

• 생명과학회지
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• 제19권7호
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• pp.923-927
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• 2009

STZ(Streptozotocin)를 이용하여 제 1형 당뇨를 유발시킨 생쥐에게 해양심층수를 음용시켜, 혈당치의 변화 및 파괴된 췌도에 미치는 영향에 대하여 연구하였다. 그 결과 수돗물을 음용시킨 생쥐에 비해서 해양심층수를 음용시킨 생쥐의 혈당이 낮아지고, 파괴되었던 췌도의 면적이 넓어졌으며, 췌도 내에 정상적인 $\beta$-세포의 수도 많아진 점으로부터, 해양심층수의 음용이 당뇨병의 증상완화에 효과가 있음이 밝혀졌다. 이러한 효과는 해양심층수에 포함된 $Mg^{2+}$의 효과인 것으로 생각되었다.

• Bulletin of the Korean Chemical Society
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• 제29권9호
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• pp.1797-1799
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• 2008