• Title/Summary/Keyword: islet cells

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Regulatory T Cells Promote Pancreatic Islet Function and Viability via TGF-β1 in vitro and in vivo (조절 T 세포 유래 TGF-β1에 의한 췌장섬세포의 기능 및 활성 증가)

  • Choi, Bongkum;Kim, Sa-Hyun
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.3
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    • pp.304-312
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    • 2018
  • Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived $TGF-{\beta}1$ on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with $4{\times}10^6$ Treg cells for 48 hours. The changes in $TGF-{\beta}1$, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P<0.0005, P<0.005) and islet viability was improved (P<0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the $TGF-{\beta}1$ secretion pathway (P<0.05~0.005), thus the use of Treg in islet transplantation should be explored further.

An immunohistochemical study of the pancreatic endocrine cells in the cat-shark, Scyliorhinus torazame (두툽상어 췌장에 출현하는 내분비세포의 면역조직화학적 연구)

  • Lee, Jae-hyun;Lee, Nam-soo;Lee, Hyeung-sik;Kim, Jong-beom
    • Korean Journal of Veterinary Research
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    • v.31 no.1
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    • pp.27-32
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    • 1991
  • The pancreatic endocrine cells of the cat-shark, S. torazame, were studied using immunohistochemical method. Five kinds of endocrine cells (glucagon-, somatostatin-, insulin-, 5-HT-and BPP-immunoreactive cells) identified in this study. The chracteristic findings of the distributions of five immunoreactive cells were as follows. Glucagon-immunoreactive cells were detected as clustering group in the epithelia of the interlobular duct and singly the pancreatic acini, respectively. Insulin -immunoreactive cells were moderately observed in the epithelia of the interlobular duct or in the periphery of the islet. Somatostatin-immunoreactive cells were distributed in single or mass groups in the epithelia of the interlobular duct and the exocrine gland of the pancreas. A very few 5-HTimmunoreactive cells were seen in the periphery of the islet and the acini of the pancreas-BPP-immunoreactive cell was singly located in the periphery of the pancreatic islet, but GAS/CCK-and Chromogranin-immunoreactive cells were not found in this study.

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Viability and Functions of Alginate-microencapsulated Islets Isolated from Neonatal Pigs

  • Lin, Yi-Juain;Wang, Jui-Ping;Chung, Yu-Tung;Sun, Yu-Ling;Chou, Yu-Chi
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.5
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    • pp.795-801
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    • 2007
  • Patients with Type I diabetes mellitus have been treated with porcine insulin for several decades and pigs have recently been deemed an ideal source of microencapsulated islet cells for clinical xenotransplantation. In this study, neonatal pigs were anesthetized and sacrificed prior to a pancreatectomy. Islet cells were isolated from pancreas via collagenase digestion. Islet cells were separated and collected by hand under microscopic guidance. These cells were suspended in 1.4% sodium alginate solution and encapsulated by dropping them into 1.1% calcium chloride solution and in which the round gel in size was 250-400 ${\mu}m$ in diameter. Viability of the microencapsulated islet cells cultured in medium at $37^{\circ}C$ was assessed by MTT assay. Furthermore, insulin released in response to glucose challenge was investigated using an enzyme-linked immunosorbent assay. Secretion of insulin was low in response to the basal glucose solution (4.4 mM) in medium and was significantly higher in response to the high glucose solution (16.7 mM). The viability of microencapsulated islet cells did not differ significantly over a period of 7 days; that is, the increasing pattern of insulin concentration in the culture medium after glucose stimulation interval day was similar throughout the 7 days cultivation. In summary, experimental evidences indicated that the effects of alginate-microencapsulation prolonged survival of the neonatal porcine islets in vitro cultures and the insulin response to glucose of the islets was maintained.

The Effects of Fetal Bovine Serum, Epidermal Growth Factor, and Retinoic Acid on Adult Rat Islets Embedded in Collagen Gels

  • Shin, Jun-Seop;Chang, Hyo-Ihl;Sung, Ha-Chin;Kim, Chan-Wha
    • Journal of Microbiology and Biotechnology
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    • v.9 no.2
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    • pp.150-156
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    • 1999
  • The induction of proliferation of adult rat islets was investigated under various culture conditions. The islets were isolated from male Sprague-Dawley rats and subsequently embedded in collagen gels, which mimic the in vivo three-dimensional surroundings. During the culture period, the effects of heterologous serum (fetal bovine serum, FBS), epidermal growth factor (EGF), and retinoic acid (RA) on islet growth were examined with respect to the morphological and total DNA content changes. To investigate these changes at the cellular level, whole mount immunocytochemistry using specific antibodies for insulin and glucagon was performed. The results showed that (i) collagen gels as an extracellular matrix can maintain islets in a similar way to that in vivo, (ii) heterologous serum (FBS) had stimulatory effects on islet proliferation in a dose-dependent manner, (iii) RA had inhibitory effects on islet proliferation induced by the serum in a dose-dependent manner, (iv) EGF had weak inhibitory effects on islet proliferation induced by the serum except at the concentration of 10 nM where its effect was not significant, and (v) whole mount immunocytochemistry revealed that newly proliferated islet cells were mainly $\beta$-and $\alpha$-cells.

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Expression of c-Jun in pancreatic islet $\alpha$-cells of nonobese diabetic(NOD) mice

  • Park, Sang-Joon;Lee, Sae-Bom;Choi, Yang-Kyu;Lee, Chul-Ho;Hyun, Byung-Hwa;Lee, Keun-Joa;Ryu, Si-Yun;Cho, Sung-Whan;Song, Jae-Chan;Lee, Cha-Soo;Jeong, Kyu-Shik
    • Korean Journal of Veterinary Pathology
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    • v.2 no.1
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    • pp.17-24
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    • 1998
  • This is the first report of c-Jun protein expression and mRNA in a pancreatic islet in a nonobese diabetic(NOD) state mice. In this experiment NOD mice with insulin-dependent diabetes mellitus type I at age 16 weeks(n=7) just before death(n=4) were used. The control group consist of prediabetic NOD(8 weeks n=7) and ICR(8 weeks n=7 and 16 weeks n=7) mice. c-Jun positive cells in the pancreatic islet of NOD mice were localized in the same positions as a-glucagon producing cells. immunoreactivity was negative in the prediabetic NOD(8 weeks) and ICR(8 weeks and 16 weeks) mice. The number of c-Jun positive cells in mice with severe diabetic state just before death were significantly decreased when compared to NOD(16 weeks) mice. Expression of c-Jun in mRNA level was assessed by RT-PCR method. The levels of mRNA in NOD(16 weeks) mice group were elevated in total pancreatic tissues. The present results suggest that the induction of proto-oncogene protein may be of significance in assessing cell specific injury and may play a functional role between pancretic islet $\alpha$-cells and $\beta$-cells in the diabetic state.

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Suitability of denervated muscle flaps as recipient sites for pancreatic islet cell transplantation

  • Park, Jong-Lim;Kim, Taewoon;Kim, Baek-Kyu
    • Archives of Plastic Surgery
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    • v.48 no.1
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    • pp.133-143
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    • 2021
  • Background Extensive research has been conducted on islet transplantation as a possible cure for diabetes. Islet transplantation in the liver via the portal vein has shown remarkable results, but numerous other recipient sites are currently being investigated. We aimed to show the effectiveness of using a muscle flap as a recipient site for islet transplantation. Methods Islet cells were harvested from 12 isogenic Lewis rats, and then diabetes was induced in another 12 isogenic Lewis rats by streptozotocin injection. In six rats, 3,000 islets were transplanted into gastrocnemius muscle flaps, and in the other six rats, the same number of islets were transplanted into the gastrocnemius muscle. The transplanted islet cell function between the two groups was compared by means of blood glucose tests, glucose tolerance tests, immunohistochemistry, and real-time reverse transcription polymerase chain reaction. Results In the muscle flap group, blood glucose levels significantly decreased after islet transplantation. Blood glucose levels were significantly different between the two groups at 3 weeks after transplantation. The muscle flap group showed nearly normoglycemic results upon the glucose tolerance test, whereas the muscle group was hyperglycemic. Immunohistochemical evaluation showed positive results against insulin and glucagon in biopsies of both groups, and the islet cell density was higher in the muscle flap group. There were no statistically significant differences between the two groups in real-time reverse transcription polymerase chain reaction results. Conclusions Our results suggest that muscle flaps are promising candidates for islet cell transplantation.

Apoptosis of Human Islet Cells by Cytokines

  • Kim, Sun-Shin;Kim, Kyoung-Ah;Suk, Kyoung-Ho;Kim, Yun-Hee;Oh, Seung-Hoon;Lee, Moon-Kyu;Kim, Kwang-Won;Lee, Myung-Shik
    • IMMUNE NETWORK
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    • v.12 no.3
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    • pp.113-117
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    • 2012
  • FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

Comparative Analysis of Phospholipase D2 Localization in the Pancreatic Islet of Rat and Guinea Pig

  • Ryu, Gyeong-Ryul;Kim, Myung-Jun;Song, Chan-Hee;Min, Do-Sik;Rhie, Duck-Joo;Yoon, Shin-Hee;Hahn, Sang-June;Kim, Myung-Suk;Jo, Yang-Hyeok
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.4
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    • pp.211-215
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    • 2003
  • To examine the localization pattern of phospholipase D2 (PLD2) in the pancreatic islet (the islet of Langerhans) depending on species, we conducted a morphological experiment in the rat and guinea pig. Since individual islets display a typical topography with a central core of B cell mass and a peripheral boundary of A, D, and PP cells, double immunofluorescent staining with a panel of antibodies was performed to identify PLD2-immunoreactive cells in the islets PLD2 immunoreactivity was mainly present in A and PP cells of the rat pancreatic islets. And yet, in the guinea pig, PLD2 immunoreactivity was exclusively localized in A cells, and not in PP cells. These findings suggest a possibility that PLD2 is mainly located in A cells of rodent pancreatic islets, and that the existence of PLD2 in PP cells is not universal in all species. Based on these results, it is suggested that PLD2 may play a significant role in the function of A and/or PP cells via a PLD-mediated signaling pathway.

Effect of the Deep Sea Water on the Blood Glucose and the Langerhans' Islet in the STZ-induced type I Diabetic Mice (해양심층수 섭취가 STZ로 유발된 제 1형 당뇨 생쥐의 혈당치 및 췌도에 미치는 영향)

  • Jung, Jae-Bong;Jung, Ji-Yoon;Yoon, Myung-Hee
    • Journal of Life Science
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    • v.19 no.7
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    • pp.923-927
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    • 2009
  • Effects of deep sea water on blood glucose and the Langerhans' islet in STZ-induced type I diabetic mice were investigated. Results showed that diabetic symptoms in STZ-induced diabetic mice improve with a supplement of deep sea water. That is, the level of blood glucose was lower, the area of the Langerhan' islet was wider, and the number of pancreatic $\beta$-cells was larger in the diabetic mice supplied with deep sea water than in the diabetic mice supplied with tap water. Such effects might be related to the high level of Mg$^{2+}$ in the deep sea water.

Cloning, Sequencing, and Characterization of Enterotoxin Pathogenicity Islet from Bacteroides fragilis 419

  • Rhie, Gi-Eun;Chung, Gyung-Tae;Lee, Yong-Jin;Sung, Won-Keun;Oh, Hee-Bok
    • Journal of Microbiology and Biotechnology
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    • v.10 no.1
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    • pp.86-90
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    • 2000
  • We have earlier reported on the cloning and identification of bft-k from an enterotoxigenic strain of Bacteroides fragilis 419, which was isolated from the blood of a Korean patient who suffered from systemic infections [4,5]. The bft-k gene encodes a 397-amino-acids metalloprotease enterotoxin, and the protein has been identified as a new isoform of B. fragilis enterotoxins (BFTs), which are cytopathic to intestinal epithelial cells to induce fluid secretion and tissue damage in ligated intestinal loops [4, 6, 18, 20]. This report describes the cloning and sequencing of the enterotoxin pahogenicity islet of B. fragilis 419 which contains the bft-k gene. the cloned enterotoxin pathogenicity islet was found to have 6,045 bp in length and to contain 120bp direct repeats near its end. In the pathogenicity islet, in addition to the BFR-K, two putative open reading frames (ORFs) were identified; (1) the t-3 gene encoding a 396-amino-acids protein of a putative metalloprotease; (2) the third gene encoding an ORF of a 59-amino-acids protein, whose function has not yet beenn characterized. The expression of the t-3 gene in B. fragilis 419 was verified by western blot analysis.

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