• Korean Journal of Veterinary Research
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• v.49 no.4
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• pp.365-368
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• 2009

A six-year-old female cocker spaniel presented with recurring episodes of pelvic limb weakness and intermittent seizures. Laboratory analysis revealed marked hypoglycemia and an elevated serum insulin concentration. A pancreatic beta-cell tumor at stage III ($T_1N_1M_1$) was diagnosed based on serial blood glucose and insulin measurements along with diagnostic imaging. The patient survived for 140 days after diagnosis with medical management, including frequent feeding and prednisolone therapy. On necropsy, necrosis and masses in the peripancreatic omentum and liver were found; pancreatic beta-cell neoplasia with metastasis to the liver was confirmed by histopathologic examination. This case reports hyper-insulinism in a dog presenting with hypoglycemic seizures.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9567-9574
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• 2014

${\beta}$-Blockers have been one of the most widely used and versatile drugs for the past half a century. A new potential for their use as anti-cancer drugs has emerged in the past few years. Various retrospective case control studies have been suggestive that use of ${\beta}$-blockers before the diagnosis of cancer could have preventive and protective effects against non-small cell lung carcinoma, melanoma, and breast, pancreatic and prostate cancers. Experimental and clinical observations are still inconclusive with some inconsistent findings. However, indications are pointing toward a positive role of some ${\beta}$-blockers against certain forms of cancers. This mini review is an effort to present the up to date published results of case-control studies and experimental findings.

• BMB Reports
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• v.51 no.10
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• pp.538-543
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• 2018

Pancreatic beta cell destruction and dysfunction induced by cytokines is a major cause of type 1 diabetes. Paraoxonase 1 (PON1), an arylesterase with antioxidant activity, has been shown to play an important role in preventing the development of diabetes in transgenic mice. However, no studies have examined the anti-diabetic effect of PON1 delivered to beta cells using protein transduction. In this study, we expressed the cell-permeable PON1 fused with PEP-1 protein transduction domain (PEP-1-PON1) to investigate whether transduced PEP-1-PON1 protects beta cells against cytokine-induced cytotoxicity. PEP-1-PON1 was effectively delivered to INS-1 cells and prevented cytokine-induced cell destruction in a dose-dependent manner. Transduced PEP-1-PON1 significantly reduced the levels of reactive oxygen species (ROS) and nitric oxide (NO), DNA fragmentation, and expression of inflammatory mediators, endoplasmic reticulum (ER) stress proteins, and apoptosis-related proteins in cytokine-treated cells. Moreover, transduced PEP-1-PON1 restored the decrease in basal and glucose-stimulated insulin secretion induced by cytokines. These data indicate that PEP-1-PON1 protects beta cells from cytokine-induced cytotoxicity by alleviating oxidative/nitrosative stress, ER stress, and inflammation. Thus, PEP-1-mediated PON1 transduction might be an effective method to reduce the extent of destruction and dysfunction of pancreatic beta cells in autoimmune diabetes.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.947-952
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• 2008

The unripe fruit of Momordica charantia (MC) has been shown to possess antidiabetic activity. However, the mechanism of its antidiabetic action has not been fully understood. In this study, the effects of the aqueous ethanolic extract of MC (AEE-MC) were evaluated on the apoptosis in pancreatic $\beta$-cells treated with a combination of the cytokines, interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-$\alpha$, and interferon (IFN)-$\gamma$. In MIN6N8 cells, the inhibitory effect of AEE-MC was significantly observed at 2 to 50 ${\mu}g/mL$: a 26.2 to 55.6% decrease of cytoplasmic DNA fragments quantified by an immunoassay. The molecular mechanisms, by which AEE-MC inhibited $\beta$-cell apoptosis, appeared to involve the inhibition on the expression of p21, Bax, and Bad, the up-regulation of Bcl-2 and Bcl-$X_L$, and the inhibition on the cleavage of caspase-9, -7, and -3 and poly (ADP-ribose) polymerase. This study suggests that MC may inhibit cytokine-induced apoptosis in $\beta$-cells and, thus, may contribute via this action to the antidiabetic influence in diabetes.

• 대한생식의학회:학술대회논문집
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• 2006.06a
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• pp.50-52
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• 2006

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.106-106
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• 2019

The leaves of Phaleria nisidai Kaneh. have been used as a beverage for tonic and immune-enhancing effect in Palau. Recently, extract of the plants showed anti-diabetic effect in clinical trial and possibility could be used as a medicine for diabetes. However, in vitro and in vivo experiments which elucidate cytotoxicity and biological mechanism have not been studied yet. To begin the series of in vitro and in vivo anti-diabetic studies, we evaluated cell viability of pancreatic beta cell lines to figure it out toxicity of the extract. The leaves of Phaleria nisidai were extracted with distilled water and 70% EtOH, and followed by evaporation and lyophilization. And, MIN6 and RIN-m5F cell lines were used for assessment of cell viability. MTT assay was adopted to evaluated a toxicity. Any of extract and concentration used in this study did not show cytotoxicity in the cell lines. Furthermore, morphological change was not observed. These results means Phaleria nisidai might be a medicinal resource when further biological and safety studies would be performed.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.559-563
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• 2003

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of $\beta$-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired $\beta$-cell function in high glucose condition. By the screening of various natural products blocking $\beta$-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced $\beta$-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of $\beta$-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.141-149
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• 2015

"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic ${\beta}$-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with $30{\mu}M$ linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.49-56
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• 2016

To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic ${\beta}$-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-${\gamma}$, IL-$1{\beta}$,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE ($20{\mu}M$) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.47-47
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• 2001

Opening of $Ca^{2＋}$ -channels represents the final common pathway for insulin secretion in pancreatic beta-cells and related cell lines. We investigated voltage-sensitive calcium channels (VSCCs) and insulin secretion in RINm5F, an insulinoma cell line derived from rat pancreatic beta-cells. Several types of VSCCs were identified in RINm5f cells： dihydropyridine-sensitive L-type, $\omega$-conotoxin GVIA-sensitive N-type, $\omega$-agatoxin IVA-sensitive P-type channels, and $\omega$-conotoxin MVIIC sensitive Q-type channels.(omitted)