• 대한생식의학회:학술대회논문집
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• 대한불임학회 2006년도 The 5th Biannual Meeting of Pacific Rim Society for Fertility and Sterility
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• pp.50-52
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• 2006

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2006년도 The 5th Biannual Meeting of Pacific Rim Society for Fertility and Sterility
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• pp.172.2-172.2
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• 2006

• The Korean Journal of Physiology and Pharmacology
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• 제7권3호
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• pp.163-168
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• 2003

The reactive oxygen species (ROS) are considered to be an important mediator in pancreatic ${\beta}$ cell destruction, thereby triggering the development of insulin-dependent diabetes mellitus. In the present study, HIV-1 Tat-mediated transduction of Cu,Zn-superoxide dismutase (SOD) was investigated to evaluate its protective potential against streptozotocin (STZ)-induced cytotoxicity in insulin-producing MIN6N cells. Tat-SOD fusion protein was successfully delivered into MIN6N cells in a dose-dependent manner and the transduced fusion protein was enzymatically active for 48 h. The STZ induced-cell destruction, superoxide anion radical production, and DNA fragmentation of MIN6N cells were significantly decreased in the cells pretreated with Tat-SOD for 1 h. Furthermore, the transduction of Tat-SOD increased Bcl-2 and heat shock protein 70 (hsp70) expressions in cells exposed to STZ, which might be partly responsible for the effect of Tat-SOD. These results suggest that an increased of free radical scavenging activity by transduction of Tat-SOD enhanced the tolerance of the cell against oxidative stress in STZ-treated MIN6N cells. Therefore, this Tat-SOD transduction technique may provide a new strategy to protect the pancreatic ${\beta}$ cell destruction in ROS-mediated diabetes.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.261-266
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• 2003

Type 1 diabetes is an organ-specific autoimmune disease caused by the cytotoxic T cells-mediated destruction of the insulin-producing beta cells in the Langerhans pancreatic islets. Hepatocyte growth factor (HGF) is a potent mitogen and a promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF via viral vector in the development of streptozotocin (STZ)-induced diabetes in mice, we have developed an adenoviral vector genetically engineered to carry the gene for human HGF (hHGF) and evaluate the change of blood glucose, insulin level, and insulin-secreting beta cells of pancreatic islets. We demonstrate that the treatment with hHGF gene prevented the development of STZ-induced diabetes and increased serum insulin level to above normal range. Furthermore, it preserved pancreatic beta cells from destruction. These in vivo results may support previous findings that HGF is insulinotropic agent for beta cells and HGF treatment renders the cells to be resistant to the development of diabetes from STZ administration. We suggest that an adenoviral mediated hHGF gene therapy is a good candidate for the prevention and treatment of type 1 diabetes.

• 한국발생생물학회지:발생과생식
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• 제11권2호
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• pp.67-77
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• 2007

최근 제 1형 당뇨병을 치료하기 위하여 인슐린-분비성 세포를 이식하는 세포대체요법이 새로운 치료법으로서 주목받고 있다. 그럼에도 불구하고 췌장세포 이식술은 이식원의 절대적인 부족으로 인해 광범위한 시행이 이루어지지 못하고 있는 실정이다. 무한증식과 전분화능을 보유하는 배아줄기세포는 이식할 $\beta$-세포의 부족을 해결할 수 있는 잠재적 세포공급원이 될 수 있을 것으로 기대된다. 본 종설에서는 인간배아줄기세포로부터 췌장 $\beta$-세포로의 유도분화방법에 관한 최근 동향을 살펴보고, 당뇨병 치료에 세포 이식술을 적용함에 있어 고려해야할 문제점 및 극복방안들을 소개하고자 한다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVI)
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• pp.220-220
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• 2005

• 한국발생생물학회지:발생과생식
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• 제23권4호
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• pp.391-399
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• 2019

Nicotinamide is used to maturate pancreatic progenitors from embryonic stem cells (ESCs) into insulin-producing cells (IPCs). It has been known that nicotinamide inhibits the enzymatic activity of SIRT1, an NAD⁺-dependent deacetylase. Here we show that SIRT1 knockdown enhances the differentiation of human ESCs into IPCs. SIRT1 knockdown enhances the clustering size of IPCs and the expression of pancreatic genes including c-peptide, pancreas/duodenum homeobox protein 1 (PDX1), insulin, somatostatin, glucagon and Nkx6.1 in human ESC-derived IPCs. In addition, We found that IPCs differentiated from SIRT1 knockdowned human ESCs have more zinc compared to those from control human ESCs. Our data suggest that SIRT1 negatively regulates the differentiation of β cells from human ESCs.

• Preventive Nutrition and Food Science
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• 제9권4호
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• pp.336-341
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• 2004

Leptin, resisitn and PAI-1 (plasminogen activator inhibitor-1) are synthesized and secreted by rodent fat cells and recently postulated to be an important link to obesity. This study was conducted to characterize the hormonal regulation of leptin, resistin, and PAI-1 gene expression in the 3T3-L1 adipocytes. The cells were treated with 0.5 $\mu$M insulin, 1 $\mu$M dexamethasone (Dex), or 0.05 $\mu$M triiodothyronine (T3) for 72 hours. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. The mRNA level of the leptin-producing ob gene was significantly increased by insulin, Dex, and T3 by 3.2-, 3.1- and 2.7-fold, respectively, compared to the control (p < 0.05). The level of resistin mRNA was increased by insulin, Dex, and T3 by 2.7-, 2.5- and 2-fold, respectively, compared to the control (p < 0.05). Likewise, the level of PAI-1 mRNA was significantly increased by insulin, Dex, and T3 compared to the control (p < 0.05). Taken together, our results suggest that insulin, Dex, and T3 may regulate the gene expression of leptin, resistin, and PAI-1 in 3T3-L1 adipocytes.

• Archives of Pharmacal Research
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• 제22권5호
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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.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2004년도 제47차 추계학술대회
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• pp.69-70
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• 2004