• BMB Reports
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• v.52 no.5
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• pp.295-303
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• 2019

Breakthroughs in stem cell technology have contributed to disease modeling and drug screening via organoid technology. Organoid are defined as three-dimensional cellular aggregations derived from adult tissues or stem cells. They recapitulate the intricate pattern and functionality of the original tissue. Insulin is secreted mainly by the pancreatic ${\beta}$ cells. Large-scale production of insulin-secreting ${\beta}$ cells is crucial for diabetes therapy. Here, we provide a brief overview of organoids and focus on recent advances in protocols for the generation of pancreatic islet organoids from pancreatic tissue or pluripotent stem cells for insulin secretion. The feasibility and limitations of organoid cultures derived from stem cells for insulin production will be described. As the pancreas and gut share the same embryological origin and produce insulin, we will also discuss the possible application of gut organoids for diabetes therapy. Better understanding of the challenges associated with the current protocols for organoid culture facilitates development of scalable organoid cultures for applications in biomedicine.

• Biomedical Science Letters
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• v.18 no.3
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• pp.193-200
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• 2012

We examined the effects of polyamines such as putrescine and cadaverine on the biosynthesis and secretion of insulin in the mouse pancreatic ${\beta}$-cell line, MIN-6. Basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS) from the MIN-6 cells were significantly increased by 20 min- or 24 h-treatment with micromolar concentrations of polyamines. To determine whether the enhancement was due to increase of insulin production by polyamines, we investigated the insulin mRNA and protein production. Both insulin mRNA and protein production were found to be not significantly affected by the polyamine treatment. Next, we examined the expression of several transcription factors (TFs) related to insulin synthesis and secretion in order to identify upstream events responsible for the promotion of insulin secretion of MIN6 cells by polyamines. Of the 6 TFs tested, MafA was induced by treatment of polyamines. MafA mRNA and protein expressions increased with treatment of polyamines. Overall results suggest that cadaverine and putrescine promote the insulin secretion process rather than the insulin biosynthesis from MIN6 cells. Also MafA may be involved in the enhanced insulin secretion process. Further studies are needed to elucidate the underlying mechanisms for promotion of insulin secretion by polyamines.

• Natural Product Sciences
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• v.22 no.3
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• pp.175-179
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• 2016

The aim of this study was to evaluate the anti-diabetic effects of the water extract of Lespedeza cuneata (LCW) using rat insulinoma (RIN) m5F cells and streptozotocin (STZ)-induced diabetic rats. The effect of LCW on the protection of pancreatic beta cells was assessed using MTT assay, and nitric oxide production was assessed using Griess reagent. STZ-induced diabetic rats were treated with 100 and 400 mg/kg body weight of LCW for 5 weeks. In results, LCW significantly protected cytokine-induced toxicity and NO production, and increased insulin secretion in RINm5F cells. LCW significantly decreased serum blood glucose, thiobarbituric acid reactive substances (TBARS), blood urea nitrogen (BUN) and advanced glycation end products (AGEs) levels, and renal fibronectin expression in STZ-induced diabetic rats. Also, LCW effectively improved BW loss in STZ-induced diabetic rats. Thus, our results suggest that LCW has a beneficial effect on cytokine-induced pancreatic beta cell damage and biomarkers of diabetic complication in hyperglycemic rats.

• 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.

• Development and Reproduction
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• v.11 no.2
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• pp.67-77
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• 2007

Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans is limited by the lack of donor organs. Therefore, generation of insulin-producing cells from human embryonic stem cells represents an attractive alternative. The present review summarizes the current knowledge on the differentiation of insulin-producing cells from human embryonic stem cells and their application to the cell therapy for treating diabetes mellitus.

• Korean Journal of Community Nutrition
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• v.17 no.2
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• pp.243-257
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• 2012

The purpose of this study was to evaluate pancreatic ${\beta}$-cell function of Korean adult and to examine the associations between ${\beta}$-cell function and nutrient intakes. Data were analyzed for 1,917 male and 2,885 female subjects older than 30 years using 'The Forth Korean National Health and Nutrition Survey in 2009'. We calculated HOMA ${\beta}$-cell (The homeostasis model assessment of ${\beta}$-cell function) using fasting glucose and fasting insulin for assessing ${\beta}$-cell function. Subjects were divided into HHG (High HOMA ${\beta}$-cell Group) or LHG (Low HOMA ${\beta}$-cell Group) according to median of HOMA ${\beta}$-cell, and then nutrient intakes were compared between two groups. In the entire study population, HHG showed lower percent of carbohydrate intakes (p < 0.05), and higher fat (p < 0.01), percent of fat (p < 0.05), vitamin A (p < 0.05), carotene (p < 0.05) and riboflavin (p < 0.05) intakes than LHG. In addition, levels of HOMA ${\beta}$-cell were negatively correlated with percent of carbohydrate (${\beta}$ = -0.040, p < 0.05), and positively correlated with percent of fat (${\beta}$ = 0.046, p < 0.01). The subjects were then divided into two subgroups according to body mass index values, either $23kg/m^2$ (under- and normal-weight) or ${\geq}23kg/m^2$ (over-weight and obese). Significant differences of some nutrients intakes and correlations with HOMA ${\beta}$-cell were observed only in under- and normal weight subjects, but not in over-weight and obese subjects. In conclusion, high carbohydrate, lower fat and lower vitamin intakes may be related with pancreatic ${\beta}$-cell dysfunction in under- and normal-weight Korean.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.422-426
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• 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.

• Journal of the Korea Convergence Society
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• v.11 no.9
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• pp.267-276
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• 2020

The purpose of this study was to investigate the relationship between VAI, insulin resistance, and pancreatic beta cell function according to the prevalence of metabolic syndrome in obese adults. From 2017 to 2019, 1,797 obese adults who received medical checkups at a general hospital in Bundang. Diagnosis of metabolic syndrome is NCEP-ATP III. HOMA index was used for insulin resistance and pancreatic beta cell function. VAI was higher in the metabolic syndrome than in the control(p<.001). As the number of risk factors for metabolic syndrome increased, the VAI value was higher(p<.001). The prevalence of metabolic syndrome increased as the VAI quartile increased(p<.001). VAI was also shown to be related to HOMA-IR and HOMA-β in the control, but not in the metabolic syndrome.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.282-287
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• 2014

We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-${\kappa}B$, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.25-31
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• 2000

ATP-sensitive potassium channels ($K_{ATP}$ channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on $K_{ATP}$ channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the $K_{ATP}$ channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was $48.6{\pm}8.4\;{\mu}M$ and the Hill coefficient was $0.73{\pm}0.11.$ Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential $(+20{\sim}+100\;mV)$ was not significantly altered by propofol $(control:\;60.0{\pm}2.7\;pS,\;0.1\;mM\;propofol:\;58.7{\pm}3.5\;pS).$ However, mean closed time was surely increased. Above results indicate that propofol blocks the $K_{ATP}$ channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.