• BMB Reports
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• v.35 no.1
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• pp.54-60
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• 2002

The effects of individual cytokine on apoptosis have been extensively studied. However, the effect of the cytokine combination, or the synergistic effect of cytokines on cell death, has not been widely studied, though synergism between cytokines has been documented in a variety of biological situations. In our effort to identify the final death effector molecule(s) in autoimmune diabetes, we inadvertently became interested in the cytokine synergism. We discovered that $IFN{\gamma}/TNF{\alpha}$ synergism, rather than the Fas ligand as currently believed, is responsible for the apoptosis of pancreatic islet cells both in vitro and in vivo. We also studied similar cytokine synergism in cancer cell deaths, and noted the similarities and dissimilarities between cancer cell death and islet cell death.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.194-198
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• 2013

Recent papers have shown that the initial event in the pathogenesis of autoimmune type 1 diabetes (T1D) comprises sensing of molecular patterns released from apoptotic ${\beta}$-cells by innate immune receptors such as toll-like receptor (TLR). We have reported that apoptotic ${\beta}$-cells undergoing secondary necrosis called 'late apoptotic' ${\beta}$-cells stimulate dendritic cells (DCs) and induce diabetogenic T cell priming through TLR2. The role of other innate immune receptors such as TLR7 or TLR9 in the initiation of T1D has also been suggested. We hypothesized that TLR2 blockade could inhibit T1D at the initial step of T1D. Indeed, when a TLR2 agonist, $Pam3CSK_4$ was administered chronically, the development of T1D in nonobese diabetic (NOD) mice was inhibited. Diabetogenic T cell priming by DCs was attenuated by chronic treatment with $Pam3CSK_4$, indicating DC tolerance. For the treatment of established T1D, immune tolerance alone is not enough because ${\beta}$-cell mass is critically reduced. We employed TLR2 tolerance in conjunction with islet transplantation, which led to reversal of newly established T1D. Dipeptidyl peptidase 4 (DPP4) inhibitors are a new class of anti-diabetic agents that have beneficial effects on ${\beta}$-cells. We investigated whether a combination of DPP4 inhibition and TLR2 tolerization could reverse newly established T1D without islet transplantation. We could achieve normoglycemia by TLR2 tolerization in combination with DPP4 inhibition but not by TLR2 tolerization or DPP4 inhibition alone. ${\beta}$-cell mass was significantly increased by combined treatment with TLR2 tolerization and DPP4 inhibition. These results suggest the possibility that a novel strategy of TLR tolerization will be available for the inhibition or treatment of established T1D when combined with measures increasing critically reduced ${\beta}$-cell mass of T1D patients such as DPP4 inhibition or stem cell technology.

• The Korean Journal of Zoology
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• v.38 no.3
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• pp.313-323
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• 1995

Ultrastructural characteristics of hemocytic differentiation pathway in Sericinus montetla Grey were observed with transmission electron microscope. Hemocytic differentiation took place in loose islets of hemopoietic organs as indicated by the presence of differentiating hemocytes; prohemocytes, plasmatocytes, granular cells and spherule cells. They are differentiatied from the stem cells through individual cell lineages. However, differentiating aspects of the oenocytoids were not observed. According to Brehelin and Zachary (1986), the premature hemocytes around the hemopoietic organs were classified into five types; prohemocytes, plasmatocytes, granular cells, spherule cells and oenocytoids.

• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.153-165
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• 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.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.684-689
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• 1996

PALMIWON is composed of 8 oriental herbs which has been known to show some pharmacological effects in kidney, blood vessels and immune systems, and used for the treatment of kid ney disease, hypertension, nervous disease and diabetic mellitus in the Orient for a long time. Based on our previous report that PALMIWON showed different effects on immune cells and ${\beta}$-cells, the immunoreactivity of ICSA (Islet Cell Surface Antibody) with ${\beta}$-cell (RINm5F) and the cell proliferation and function of interleukin-1${\beta}$ damaged ${\beta}$-cells in the presence of PALMIWON were examined. It was observed that PALMIWON significantly inhibited the immunoreactivity of ICSA with ${\beta}$-cell, and markedly increased cell proliferation and insulin release of interleukin-1${\beta}$ damaged ${\beta}$-cells.

• YAKHAK HOEJI
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• v.29 no.3
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• pp.152-158
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• 1985

In order to investigate the antidiabetogenic activity of T. kirilowii on the alloxan-treated mice, the effects of the oral administration of the methanol extract on the blood glucose, the survival rate and the histological changes of the Langerhans' islet were observed. The blood glucose was reached at the highest levels of $265.03\pm15.07$ and $186.41\pm0.16mg/dl at 30 min after alloxan injection, and at the lowest levels of $43.35\pm5.28$ at 4 hour and $20.40\pm3.264mg/dl at 10. hour in experimental and control group, respectively. 57.15% of the experimental group and 4.2%, of the control group were survived more than 24 hours. The life spans of the mice, which were dead within 24 hours, were $631.45\pm60.17$ for the experimental group and $414.60\pm36.24$ min for the control group. The mice from the control group, which were dead within 10 hours, showed totally necrotized $\alpha$- and $\betha$-cells. However, 3 of the 10 mice from the experimental group, which were survived until 24 hours, showed a normal histological feature of the Langerhans' islet.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.522-524
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• 1999

A discontinuous Percoll gradient was used to separate islets from the collagenase-treated mouse pancreas easily and rapidly. Since the osmolality of Percoll is very low, adjustment of its osmolality to 340 mOs/kg $H_2$O was essential for securing the optimal separation. A discontinuous gradient layering with Percoll solution of 1.09 g, 1.07g, and1.05g/m, respectively, when centrifuged at 800$\times$g for 10 min, resulted in an optimal condition for separation and yielded a banding pattern with an even distribution of islet cells. No significant difference was observed in the morphological features between the Percoll-isolated and the manually-isolated islets. In conclusion, the discontinuous Percoll gradient can be effectively used to isolate the pancreatic islets from mice with four-fold higher efficiency compared to the handpicking method.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.235-239
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• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1628-1634
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• 2004

This study was aimed to verify the anti-diabetic activity of Kangdangboeumbang(KBB) in NOD mice which is Insulin Dependent Diabetes Mellitus(IDDM). The reduction of blood glucose after oral administration between 14 weeks by 2 weeks period to a NOD mice in KBB extract treatment group was showed from 7 day after comparing with control group. KBB extract treatment group increasd insulin secretion amount of serum than control group and decreased IFN­γ production. The pancreatic β-cells is destroyed by Th1-dependent autoimmune disease in NOD mice. KBB extract treatment group intercepted the progress of edematous islet controlling inflammatory mononuclear cells of infiltration that also destruction of pancreatic β-cells electively in a NOD mice.

• The Journal of Korean Medicine
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• v.22 no.4
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• pp.79-89
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• 2001

Objectives : This study has been carried out to investigate the effects of the Saengjinyanghyutang-gamibang and Rosa rugosa extracts on pancreas of the hyperglycemia mice induced with streptozotocin. Methods : We examined immunohistochemistry for insulin and COX-2, ultrastructural changes of acini by electron microscope, and changes of the blood glucose and BUN levels. Results : The ${\beta}-cells$ on Langerhnan's islet were destructed by administration of streptozotocin, so that few insulin-positive cells were observed in the control group. However, a lot of insulin-positive cells were observed in the experimental groups. These cells had recovered from the damage. As a result of COX-2 immunostain, COX-2 expression were highest in the control group other than the Saengjinyanghyutang-gamibang and Rosa rugosa extracts administered groups. As the electron microscopical observation, the centroacinar cells and acini of pancreas were destructed or damaged by administration of streptozotocin in the control group, but these recovered !Tom the damage in the other experimental groups. The levels of serum glucose were decreased remarkably on the Rosa rugosa and Saengjinyanghyutang-gamibang extracts administered groups compared with control group. Conclusions : These results suggest that administration of the Rosa rugosa and Saengjinyanghyultang-gamibang extracts to the mice reduced the damage induced by streptozotocin.