• IMMUNE NETWORK
• /
• 제13권6호
• /
• pp.235-239
• /
• 2013

Encapsulation of tissue has been an area of intense research with a myriad number of therapeutic applications as diverse as cancer, tissue regeneration, and diabetes. In the case of diabetes, transplantation of pancreatic islets of Langerhans containing insulin-producing beta cells has shown promise toward a cure. However, anti-rejection therapy that is needed to sustain the transplanted tissue has numerous adverse effects, and the islets might still be damaged by immune processes. Furthermore, the profound scarcity of healthy human donor organs restricts the availability of islets for transplant. Islet encapsulation allows the protection of this tissue without the use of toxic medications, while also expanding the donor pool to include animal sources. Before the widespread application of this therapy, there are still issues that need to be resolved. There are many materials that can be used, differing shapes and sizes of capsules, and varied sources of islets to name a few variables that need to be considered. In this review, the current options for capsule generation, past animal and human studies, and future directions in this area of research are discussed.

• 동의생리병리학회지
• /
• 제22권2호
• /
• pp.422-426
• /
• 2008

In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced ${\beta}-cell$ death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of ${\beta}-cell$ destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with $interleukin-1{\beta}$ ($IL-1{\beta}$) and $interferon-{\gamma}$ ($IFN-{\gamma}$) resulted in a reduction of cell viability. RTE protected $IL-1{\beta}$ and $IFN-{\gamma}$-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of $IL-1{\beta}$ and $IFN-{\gamma}$-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of $NF{-\kappa}B$ activation. The $IL-1{\beta}$ and $IFN-{\gamma}$-stimulated RIN cells showed increases in $NF{-\kappa}B$ binding activityand $I{\kappa}B{\alpha}$ degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced $I{\kappa}B{\alpha}$ degradation and $NF{-\kappa}B$ activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in $IL-1{\beta}$ and $IFN-{\gamma}$-treated islets.

• 대한수의학회지
• /
• 제2권1호
• /
• pp.1-13
• /
• 1962

10두(頭)의 홀스타인 자우(仔牛)에 glucagon, insulin 등 홀몬과 reserpine 및 nicotine을 투여(投與)하여 그들이 췌장(膵臟)의 Langerhans 도서(島嶼)에 미치는 세포학적(細胞學的) 영향을 전자현미경(電子顯微鏡)에 의해서 연구하는 도중 거대(巨大)한 크기의 도서(島嶼)를 관찰하였다. 이 거대도서(巨大島嶼)들은 상기(上記)한 약품투여에 영향을 받지 않으며 거의 beta 세포(細胞)들로만 되어 있으므로 보통 크기의 도서(島嶼)들과의 혼동을 피하기 위하여서는 그 분포상태(分布狀態)와 세포학적(細胞學的) 및 조직학적(組織學的) 특징(特徵)을 구명(究明)하는 것이 필요하게 되어 본연구(本硏究)에 착수하였든 것이며 아울러 췌장(膵臟) 각부분(各部分)에 함유되는 Langerhans 도서수(島嶼數)의 평균치(平均値)를 산출(算出)하였다. Langerhans 도서(島嶼)는 편의상 그 크기에 따라서 직경(直徑) $200{\mu}$이하(以下)의 것을 "Regular islets" $200{\sim}500{\mu}$까지의 것을 "Intermediate islets" 그리고 $500{\mu}$ 이상(以上)의 것을 "Giant islets"라 이름지어서 구별하였다. 지금까지 알려진 최대(最大)의 도서(島嶼)는 개에서 관찰된 $333{\mu}$의 도서(島嶼)이었는데 필자는 본연구(本硏究)에서 직경 $1.395{\mu}$에 달하는 것과 기리 $2,700{\mu}$에 달하는 거대(巨大)한 도서(島嶼)들을 관찰하였다. 본연구(本硏究)의 결과(結果)를 요약(要約)하면 다음과 같다. 1. 자우췌장(仔牛膵腸) 50평방(平方)mm 면적(面積)내에 함유되는 Langerhans 도서(島嶼)의 수(數)는 평균(平均) 191개로서 다른 연구자에 의해서 보고된 수치(數値)보다 훨씬 많은 것이었다. 2. 거대도서(巨大島嶼)의 크기는 직경(直徑) $200{\sim}1,400{\mu}$이며 그 분포상태(分布狀態)는 보통 크기의 도서(島嶼)와 마찬가지로 췌장(膵臟)의 십이지장부(十二指腸部) 중간부(中間部) 및 췌장부(膵臟部)의 순서(順序)로 많이 함유되고 있다. 즉 십이지장부(十二指腸部)에는 2% 중간부(中間部) 1.8% 췌장부(膵臟部)에는 0.8%의 거대도서(巨大島嶼)가 함유되어 있으며 직경(直徑) $200{\mu}$이상(以上)의 도서평균치(島嶼平均値)는 1.53%이었다. 3. 중간대(中間大)의 도서(島嶼)와 거대도서(巨大島嶼)들은 거의 beta 세포(細胞)들로서만 되어있음으로 "중간대(中間大) beta 도서(島嶼)" 및 "거대(巨大) beta 도서(島嶼)"라고 각 각 명명하였으며 alpha세포(細胞)들이 있는 경우에는 작은 세포집합체(細胞集合體)를 이루고 도서전반(島嶼全般)에 걸쳐서 산재(散在)한다. 4. 췌장(膵臟)에 함유되고 있는 거대(巨大) beta 도서(島嶼)의 수(數)는 적지마는 보통 크기의 도서(島嶼)와 비교할때 그 용량(容量)은 막대한 것이며 따라서 insulin 분비량(分泌量)도 많을것이므로 우췌장(牛膵臟)의 insulin 분비(分泌)를 연구할 때에는 반듯이 이 사실(事實)을 고려해야 할 것이다. 5. 불규칙한 색상(索狀)의 실질세포(實質細胞)들로된 거대(巨大) beta 도서(島嶼)에는 간질결합조직(間質結合組織)이 풍부하며 그 간질(間質) 속에는 비교적 큰 혈관(血管)과 개재관양(介在管樣) 구조물(構造物)이 들어있다. 거대(巨大) beta 도서(島嶼)는 출생(出生)후 도서내외(島嶼內外)에 산재(散在)하고 있는 외분비도관세포(外分泌導管細胞)들의 증식(增殖)에 의해서 발생(發生)하며 그 크기도 증대(增大)하는 것으로 믿어진다. 6. 거대(巨大) beta 도서(島嶼)의 beta 세포(細胞)들은 현저한 Golgi 장치(裝置)와 비대(肥大)한 핵소체(核小體) 및 포상핵(胞狀核)등의 세포학적(細胞學的) 특징을 가지며 이것은 거대(巨大) beta 도서(島嶼)가 보통 크기의 Langerhans 도서(島嶼)에 비하여 더 활발하게 insulin을 분비(分泌)한다는 것을 시사(示唆)하는 것이다.

• 동의생리병리학회지
• /
• 제22권2호
• /
• pp.340-345
• /
• 2008

Extract of Acanthopanax senticosus has recently been demonstrated to possess significant antidiabetic potential, in accordance with the traditional use of this plant as an antidiabetic natural health product. The present study evaluated the effects of fermented extract (FE) of this plant on glucose-stimulated insulin secretion, glucose uptake, and streptozotocin-induced type 1 diabetes model. A 3 h pretreatment with FE prevented $IL-1{\beta}$ and $IFN-{\gamma}$ toxicity in isolated rat islets. However, it did not affect insulin-stimulated glucose uptake in C2C12 myotubes. In addition, pretreatment of mice with FE blocked the destruction of streptozotocin-induced islets and the development of type 1 diabetes. FE reduced blood glucose level, increased insulin secretion, and improved glucose tolerance in streptozotocin-treated mice, whereas nonfermented extract (NFE) had moderate effects. Immunohistochemical staining for insulin clearly showed that pretreatment with FE blocked the STZ-induced islets destruction and restored the number of islet cells that secreted insulin to the level of the control. Although the active principles and their mechanisms of action remain to be identified, FE may nevertheless represent a novel complementary therapy and a source of novel therapeutic agents against type 1 diabetes mellitus.

• BMB Reports
• /
• 제44권11호
• /
• pp.713-718
• /
• 2011

In this study, the effects of sitagliptin analogue (SITA) or pioglitazone (PIO) treatment on glucose homeostasis and ${\beta}$-cell dynamics in animal models of type 2 diabetes-Akita and db/db mice were evaluated. After 4-6 weeks of treatment, both SITA and PIO were shown to lower non-fasting glucose levels and reduced glycemic excursion in the intraperitoneal glucose tolerance test. In addition, both drugs preserved normal islet structure and the proportion of ${\beta}$-cells in the islets. Compared to the controls, SITA treatment induced a higher ${\beta}$-cell proliferation rate in Akita mice and a lower rate of apoptosis in db/db mice, whereas PIO treatment induced a lower rate of apoptosis in db/db mice and reduced proliferation rates in Akita mice. In conclusion, both SITA and PIO appear to exert some beneficial effects on the islet structure in addition to glycemic control via different mechanisms that involve ${\beta}$-cell dynamics in Akita and db/db mice.

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

• Journal of Korean Neurosurgical Society
• /
• 제62권2호
• /
• pp.153-165
• /
• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• 대한임상검사과학회지
• /
• 제50권3호
• /
• pp.304-312
• /
• 2018

본 연구에서는 면역 억제 역할을 하는 것으로 알려져 있는 조절 T 세포 (regulatory T cell, Treg)의 새로운 생리학적 기능 대하여 확인해보고자 하였다. 시험관내나 동물실험에서 조절 T 세포가 분비하는 transforming growth factor ${\beta}1$ ($TGF-{\beta}1$)에 의하여 이식 직전까지 췌장섬세포의 생존률을 향상시키면서 동시에 혈당조절 기능이 향상될 수 있을 것이라는 가설이다. 이를 증명하기 위하여 마우스를 이용한 1형 당뇨병 모델을 제작한 뒤, 180 IEQ (islet equivalents)의 췌장섬세포를 동종간 이식하였다. 췌장섬세포는 이식 수술 시행 전까지 48시간 동안 $4{\times}10^6$의 Treg 세포와 함께 배양하여 Treg 유래 $TGF-{\beta}1$에 충분히 노출시킨 뒤 사용하였다. Treg 단독군, 췌장섬세포 단독군 및 Treg/islet 동시 배양군에서 각각 $TGF-{\beta}1$, IL-6 및 인슐린 분비 수준의 변화를 측정하였다. Treg/islet 동시 배양군에서 IL-6와 인슐린 분비는 증가하였고 (P<0.0005, P<0.005), 췌장섬세포 단독군과 비교하여 생존율이 향상되었다(P<0.005). 또한, 이식 후, 동시 배양된 췌장섬세포는 1형 당뇨병 마우스 모델에서 혈당 수치를 보다 효율적으로 조절하였다. 이러한 결과는 Treg 세포가 $TGF-{\beta}1$ 분비를 통하여 췌장섬세포의 기능과 생존력을 향상시킬 수 있음을 시사한다.

• Biomolecules & Therapeutics
• /
• 제22권1호
• /
• pp.47-54
• /
• 2014

The present study was aimed to evaluate the antioxidant defense system of cinnamaldehyde in normal, diabetic rats and its possible protection of pancreatic ${\beta}$-cells against its gradual loss under diabetic conditions. In vitro free radical scavenging effect of cinnamaldehyde was determined using DPPH (1,1-diphenyl-2-dipicrylhydrazyl), superoxide radical, and nitric oxide radical. Streptozotocin (STZ) diabetic rats were orally administered with cinnamaldehyde at concentrations of 5, 10 and 20 mg/kg body weight for 45 days. At the end of the experiment, the levels of plasma lipid peroxides and antioxidants such as vitamin C, vitamin E, ceruloplasmin, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase were determined. A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, and lipid peroxides and significant decrease in the levels of plasma insulin and reduced glutathione were observed in the diabetic rats. Also the activities of pancreatic antioxidant enzymes were altered in the STZ-induced diabetic rats. The altered enzyme activities were reverted to near-normal levels after treatment with cinnamaldehyde and glibenclamide. Histopathological studies also revealed a protective effect of cinnamaldehyde on pancreatic ${\beta}$-cells. Cinnamaldehyde enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects pancreatic ${\beta}$-cells against their loss and exhibits antidiabetic properties.

• 대한한방내과학회지
• /
• 제28권3호
• /
• pp.510-518
• /
• 2007

Objectives : The aim of this study was to investigate the effect of Jaeumyangyung-tang(滋陰養榮場(JY), JA-0.65g/kg;JB-1.3g/kg) on hyperglycemic mice induced with streptozotocin(STZ). Methods : The experiment operated for 6 weeks. The rats were divided into 3 groups : diabetic group(control group), diabetic group treated with JA(0.65g/kg) for 6 weeks, and diabetic group treated with Jb(1.3g/kg) for 6 weeks. Results : In the STZ-induced diabetic group, blood glucose levels significantly increased as well as the loss of body weight. The levels of serum glucose decreased significantly (p<0.05 or p<0.01) in the JA and JB groups compared with the control. According to a tolerance test, intraperitoneal glucose was ameliorated in the JA and JB groups. The blood urea nitrogen (BUN) and creatinine levels slightly decreased. Histologic analyses of the pancreases revealed that the ${\beta}-cells$ on Langerhans' islets were destroyed by STZ, but the ${\beta}-cell$ mass was larger in the JY than in the control mice. Conclusions : These results indicate that JY can exert beneficial effects on diabetes. preservation of in vivo ${\beta}-cell$ function and regeneration of ${\beta}-cell$ dysfunction by STZ.