• 공업화학
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• 제20권6호
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• pp.581-585
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• 2009

당뇨병은 인슐린 분비가 부족하거나 그 인식 기능이 감소하여 발생하는 만성질환으로, 현재까지도 완전한 치료법은 개발되지 못하고 있다. 그 중 제I형 당뇨병에 가장 많이 쓰이는 치료법은 인슐린 주사로 알려져 있다. 하지만 인슐린 주사는 때로 치명적인 위험과 불편함을 수반하므로, 이를 개선하기 위한 많은 연구들이 수행되고 있다. 이러한 방법의 일환으로, 자가 조절 인슐린 전달 시스템이 제안되었다. 본 총설에서는 현재까지 연구되고 있는 대표적인 자가 조절 인슐린 전달 시스템의 포도당 응답성 방출 원리에 대해 살펴보고자 한다.

• IMMUNE NETWORK
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• 제16권5호
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• Genomics & Informatics
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• 제13권3호
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• pp.76-80
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• 2015

Type 2 diabetes mellitus is a complex metabolic disorder associated with multiple genetic, developmental and environmental factors. The recent advances in gene expression microarray technologies as well as network-based analysis methodologies provide groundbreaking opportunities to study type 2 diabetes mellitus. In the present study, we used previously published gene expression microarray datasets of human skeletal muscle samples collected from 20 insulin sensitive individuals before and after insulin treatment in order to construct insulin-mediated regulatory network. Based on a motif discovery method implemented by iRegulon, a Cytoscape app, we identified 25 candidate regulons, motifs of which were enriched among the promoters of 478 up-regulated genes and 82 down-regulated genes. We then looked for a hierarchical network of the candidate regulators, in such a way that the conditional combination of their expression changes may explain those of their target genes. Using Genomica, a software tool for regulatory network construction, we obtained a hierarchical network of eight regulons that were used to map insulin downstream signaling network. Taken together, the results illustrate the benefits of combining completely different methods such as motif-based regulatory factor discovery and expression level-based construction of regulatory network of their target genes in understanding insulin induced biological processes and signaling pathways.

• 한국고분자학회지:고분자과학과기술
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• 제22권5호
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• pp.439-446
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• 2011

• 생명과학회지
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• 제31권11호
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• pp.969-979
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• 2021

당뇨병은 만성대사성 질환으로 우리나라 국민의 사망요인 중 5위를 차지하고 있다. 제 2형 당뇨병에서 나타나는 인슐린 분비 감소는 베타세포의 자가사멸에 의한 베타세포질량의 급격한 감소로 인한 것으로 보고되고 있으며, 베타세포의 자가사멸을 촉진하는 요인으로 고혈당에 의한 당독성 및 활성산소종들의 증강에 의한 산화스트레스 등이다. 벼메뚜기 추출물은 고농도 포도당 처리된 INS-1 췌장 베타 세포에서 세포 생존율을 증가시키고, 지질과산화물, 세포 내 ROS 및 NO 수준을 감소시켰다. 세포사멸 관련 인자의 유전자 발현 결과 pro-세포자가사멸인자인 Bax, Cytochrome C, caspase-3 및 caspase-9의 단백질 발현을 유의적으로 감소시켰고, anti-세포자가사멸인자인 Bcl-2 발현을 증가시켰다. Annexin V/I propidium iodide 염색법을 통하여 벼메뚜기 추출물이 고농도 포도당으로 유도된 세포 사멸을 감소시키고, INS-1 췌장 베타세포에서의 인슐린 분비능을 증가시키는 것으로 사료된다. 그러므로 벼메뚜기 추출물이 고농도 포도당으로 손상된 INS-1 췌장 베타세포의 보호효과를 나타낸다. 본 연구의 결과는 벼메뚜기 추출물이 당뇨병 치료에 도움을 주는 항당뇨 기능성 식품 소재 및 개발에 기여할 수 있음을 시사한다.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.99-99
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• 2002

The hormone resistin is associated with typeII diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downregulates a resistin which is induced during adipocyte differentiation. But the connection between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin cDNA and to generate transgenic mice overexpressing mouse resistin gene. The 555 bp of mouse resistin was amplified from mob cDNAS by polymerase chain reaction (PCR) and cloned into pCR$\^$(R)/ 2.1 TOPO T-vector. Mouse resistin mRNA on the basis of Genbank sequence (acession no. AF323080). Then, the PCR product was cloned into pTargeT$\^$TM/ mammalian expression vector that has pCMV promoter and chimeric intron. Restriction enzyme analysis with BamH I and Not I was carried out to determine an orientation of the insert in the vector. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$\^$TM/-mus/resistin by digestion of Bgl II, and has used for microinjection into pronuclei of one cell embryos. The microinjected embryos were transfered to pseudopregnant foster-mother. Mouse resistin expression was detected in transgenic F1 mice by Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR). Resistin gene expression mouse has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, the abdominal fat pads were isolated from each 24h starvation and re-feeding after fasting group mice that were assessed by RT-PCR analysis. In fasting group mice, resistin expression was higher than that of re-feeding group mice. This result suggests that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes mellitus caused by insulin resistance of resistin.

• 대한의생명과학회지
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• 제15권3호
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• pp.207-215
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• 2009

We carried out this study to investigate differences of physiological variables between patients with (DM group) and without type II diabetes mellitus (Non-DM group) undergoing off-pump coronary artery bypass grafting (OPCABG). Postoperative $Mg^{++}$ and $Ca^{++}$ levels were lower, whereas $Na^+$ level was higher in DM group than those in Non-DM group. ICU (intensive care unit) stay time in DM group was longer than that of Non-DM group. Postoperative platelet counts tended to decrease, whereas C-reactive protein (CRP) and cardiac troponin-I (cTNI) levels tended to increase in DM group compared with Non-DM group. Postoperative albumin level was lower, while blood urea nitrogen (BUN) and creatinine levels were greater in DM group than those in Non-DM group. DM group had higher incidence of post-operative arrhythmias than Non-DM group. These results reveal that type II DM patients undergoing OPCAB may have higher incidences of postoperative hypomagnesemia, hypocalcemia and arrhythmias, and increases of CRP, cTNI, BUN, and creatinine levels than in Non-DM patients undergoing OPCAB. The perioperative check and control (supplement) of $Mg^{++}$ levels should be considered in cardiovascular surgery combined with DM.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.81-81
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• 2003

Glibenclamide, a sulfonylurea derivative, has been used in tile treatment of type II diabetes mellitus. Recent studies provided evidence that glibenclamide, in addition to blocking ATP-sensitive $K^{+}$ channels, also affected Na$^{+}$-K$^{+}$ pumps and L-type $Ca^{2+}$ channels in noncardiac cells. The effect of glibenclamide on the cardiac muscle is not clearly known. In the present study, the effects of glibenclamide on intracellular Na$^{+}$ concentration ([Na$^{+}$]$_{i}$ ), twitch tension, $Ca^{2+}$ transient, and membrane potential were investigated in isolated guinea-pig ventricular myocytes. Glibenclamide at concentration of 200 $\mu$M increased [Na$^{+}$]$_{i}$ by 3.9$\pm$0.4 mM (mean $\pm$ SE, n=12), decreased twitch tension by 36.1 $\pm$ 4.0％ (mean $\pm$ SE, n=8), reduced $Ca^{2+}$ transient by 24.4$\pm$5.1％ (mean $\pm$ SE, n=3), slightly depolarized diastolic membrane potential, and did not change action potential duration. To determine whether inhibitions of Na$^{+}$-K$^{+}$ pumps and L-type $Ca^{2+}$ channels are responsible for the increase of [Na$^{+}$]$_{i}$ and the decrease of twitch tension, we tested effects of glibenclamide on Na$^{+}$-K$^{+}$ pump current and L-type $Ca^{2+}$ current. Glibenclamide decreased Na$^{+}$-K$^{+}$ pump current and L-type $Ca^{2+}$ current in a concentration-dependent manner.t in a concentration-dependent manner.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3071-3074
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• 2014

Background: To investigate the related risk factors of postoperative nosocomial pneumonia (POP) in patients withI-IIIa lung cancer. Methods: Medical records of 511 patients who underwent resection for lung cancer between January 2012 to December 2012 were retrospectively reviewed. Risk factors of postoperative pneumonia were identified and evaluated by univariate and multivariate analyses. Results: The incidence of postoperative pneumonia in these lung cancer patients was 2.9% (15 cases). Compared with 496 patients who had no pneumonia infection after operation, older age (>60), histopathological type of squamous cell carcinoma and longer surgery time (>3h) were significant risk factors by univariate analysis. Other potential risk factors such as alcohol consumption, history of smoking, hypersensitivity, hypertension, diabetes mellitus and so on were not showed such significance in this study. Further, the multivariate analysis revealed that old age (>60 years) (OR 5.813, p=0.018) and histopathological type of squamous cell carcinoma (OR 5.831, p<0.001) were also statistically significant independent risk factors for postoperative pneumonia. Conclusions: This study demonstrated that being old aged (>60 years) and having squamous cell carcinoma histopathological type might be important factors in determining the risk of postoperative pneumonia in lung cancer patients after surgery.

• Genomics & Informatics
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• 제12권4호
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• pp.181-186
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• 2014

Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.