• 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.

• Korean Journal of Food Science and Technology
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• v.38 no.5
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• pp.679-683
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• 2006

The effects of dried and fermented guava (Psidium guajava L.) leaf extracts on blood glucose levels were investigated in low-dose streptozotocin(STZ)-induced diabetic mice. Fermented guava leaf extract (500 mg/kg/day) significantly decreased the fasting blood glucose levels after 2-4 weeks of treatment and improved the impaired glucose tolerance in STZ-induced diabetic mice. On the other hand, dried guava leaf extract lowered the blood glucose levels and improved glucose tolerance two weeks after treatment, but exacerbated STZ-induced high blood glucose levels three and four weeks after treatment. Histological and immunohistochemical observation showed that fermented guava leaf extract treatment improved STZ-induced pancreatic beta-cell damage, but dried guava leaf extract did not affect the damage to the beta-cells. These results suggest that fermented guava (Psidium guajava L.) leaf extracts improve the hyperglycemia by protecting the pancreatic beta-cells hom damage in STZ-induced diabetic mice.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.95.1-95.1
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• 2003

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved evidently as a potential remedy for type 2 diabetes mellitus. Both in vivo and in vitro experiments with water extract of Sopungsungi-won have been reported to exhibit anti-diabetic effects in our previous studies. In the present study, we have chosen Rheum undulatum (RU), which is the main component of Sopungsungi-won, to examine its anti-apoptotic effect on pancreatic b-cells, HIT-T15, against oxidative stress induced by hydrogen peroxide (H$_2$O$_2$). (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.126-126
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• 1998

Studies on natural products are of great interest, due to the limits in development of synthesized medicine and its side effects. Deer antler is the most popular cure-all type drug among Asian folk medicines. In this study, we newly isolated the biologically active components from chloroform extract and 70% ethanol extract of deer antler, and analyzed their structures. First, the structure of monoacetyldiglyceride in deer antler was identified. To investigate the structure-activity relationship of monoacetyldiglycerides, we synthesized diverse substituted glycerides from glycerol, and confirmed their structures by spectroscopic methods. Among seven structurally-interesting compounds tested in this study, compound 1,2,3,5, and 6 showed activity toward [Ca$\^$2+/]$\_$i/ increase in fura-2 loaded rat pancreatic acinar cells. Second, 70% ethanol extract of deer antler stimulated insulin release from rat pancreatic islets. We found the most effective fraction was CN-Es-8 in 70% ethanol extract, and it increased intracellular Ca$\^$2+/ concentration in pancreatic ${\beta}$-cell.

• Journal of Life Science
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• v.34 no.1
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• pp.9-17
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• 2024

Diabetes mellitus (DM) is one of the main global health problems. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic β-cell is that the characteristic decreases in insulin secretion are caused by regulated apoptotic gene expression. In this study, we examined whether ferulic acid protects INS-1 pancreatic cells against high glucose-induced apoptosis. High glucose concentration (30 mM) induced glucotoxicity and death of INS-1 pancreatic β cells. However, treatment with 1, 5, 10, or 20 μM ferulic acid increased the cell viability in a concentration-dependent manner. Treatment with ferulic acid dose-dependently decreased the intracellular levels of reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide in INS-1 pancreatic β cells pretreated with high glucose. These effects influence the apoptotic pathway, increasing the expression of the anti-apoptotic protein Bcl-2 and reducing the levels of pro-apoptotic proteins, including Bax, cytochrome C, and caspase 9. Annexin V/propidium iodide staining indicated that ferulic acid significantly reduced high glucose-induced apoptosis. These results demonstrate that ferulic acid is a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.

• Korean Journal of Plant Resources
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• v.25 no.2
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• pp.184-192
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• 2012

The present study was designed to examine the potential antidiabetic and antioxidant effect of ethanol extract from $Prunus$ $mume$ fruit (PME) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. To evaluate the antidiabetic effect of PME, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide (MTT) cell proliferation assay, lactate dehydrogenase (LDH) release assay, $NAD^+$/NADH ratio and insulin secretion were assessed. We also measured its antioxidant effect against alloxan-induced oxidative stress in the cells by assessing the levels of the antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$ /NADH ratio and insulin secretion in HIT-T15 cells. However, PME significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular $NAD^+$ /NADH ratio and insulin secretion were also increased by 1.5~1.9-fold and 1.4-fold, respectively, after treatment with the PME. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while PME significantly elevated the levels of antioxidant enzymes. Based on these results, we suggest that PME could have a protective effect against the cytotoxicity and dysfunction of pancreatic ${\beta}$-cells in the presence of alloxan-induced oxidative stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.468-473
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• 2007

The antidiabetic effect of Amomum xanthioides(A. xanthioides) extract was investigated. Alloxan caused the hyperglycemia and hypoinsulinemia by a selective destruction of pancreatic ${\beta}$-cell. Pretreatment of mouse with A. xanthiodies extract for 2 days prior to alloxan administration completely protected hyperglycemia induced by alloxan. In addition, administration of A. xanthioides extract to alloxan-induced diabetic mouse significantly abolished hyperglycemia, hypoinsulinemia, and, the reduction of size and number of insulin-secreting cells induced by alloxan. Administration of A. xanthioides extract to alloxan-induced diabetic mouse rapidly increased pancreatic Reg gene expression to 7 days, and then decreased. In alloxan-diabetic mouse. Reg gene expression was increased at 3 days after alloxan injection, and sustained until 24 days. The present results indicate that A. xanthioides extract contains potentially effective components exhibiting both protection and treatment of alloxan-induced diabetes. These results suggested that the antidiabetic effect of A. xanthoides extract may be mediated through the regeneration of pancreatic ${\beta}$-cells.

• Journal of Life Science
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• v.22 no.7
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• pp.904-911
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• 2012

Yacon has been used in folk medicines as a medicinal tea for hypoglycemia treatment. In a recent study described herein, antioxidative, antibacterial, antifungal activities, and cell-protective functions of yacon leaves have been reported. To evaluate the effects on fibrosis on pancreatitis, the efficacy of 1% of yacon extract (YE) on dibutyltin dichloride (DBTC) (8 mg/kg)-induced pancreatitis in rats was examined. On the 21st day after the DBTC treatment, a large increase in collagen was observed in the pancreas in the DBTC-treatment group (DT). But this was noticeably decreased with YE. In relation to the expression of COX-2, there was no response or a very weak response in the pancreas of the control group (CON). However, in DT, strong expression of COX-2 was observed in the pancreas on the 14th day, and COX-2 was present in inflammatory cells in the pancreas of the DT, especially on the 21st day. The expression was decreased for YE compared with DT. A remarkable increase in TGF-${\beta}1$ expression was observed in inflammatory cells in the pancreas in DT on the 21st day, whereas the expression was not found in YE after 21 days. However, on the 21th day, TGF-${\beta}1$ expression was increased in acinar cells of YE compared with DT. VEGF expression was very similar to the expression of in the pancreas. These results suggest that YE has an inhibitory effect on DBTC-induced pancreatic fibrosis.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.923-931
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• 2002

Sopungsungi-won (SP) is a known for\mula for senile constipation and diabetes mellitus, based on traditional Korean medicine. The preventive effect of SP on the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was evaluated. When administered orally through a diet for 8 weeks, diabetic conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all ameliorated in SP-treated rats. In parallel with the onset and progression of hyperglycemia in the ZDF control rats; there was a marked decline in plasma insulin concentrations from 26.1 $\mu$U/ml, at age 7 weeks, to 14.8 $\mu$U/ml at age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations did not decline, and SP at a dose of 5 g/kg significantly increased the insulin levels to 31.9 $\mu$U/ml. Early normalization of plasma insulin and a retained ability to subsequently increase plasma insulin were indicative of a pancreatic $\beta$ cell protective action by the SP for\mula. In addition, expressions of an insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4), in skeletal \muscle, were also determined in SP- and rosiglitazone-treated ZDF rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the SP for\mula, the activity of glucose-6-phosphatase was decreased by 49%, whereas the activity of glucokinase was increased by 196%, compared to the ZDF control rats. Taken together, these data provide evidence that the SP for\mula markedly lowered the plasma glucose levels, probably through an effect not only on improvement of insulin action, but through a combined sti\mulation of glycolysis and an inhibition of gluconeogenesis in the liver, and also suggest the validity of SP's clinical use in the treatment of type 2 diabetes mellitus following further toxicological investigation.

• Journal of Acupuncture Research
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• v.26 no.5
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• pp.39-47
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• 2009

목적 : 정상 췌장조직 속에 존재하는 췌장 소도세포들을 파괴시켜 고혈당을 유발시키고 복령 물추출물로 약침을 시술하여 췌장 조직의 보호효과와 항당뇨 효과를 살펴보고자 실험을 진행하였다. 방법 : 5주령의 Sprague-Dawley rat을 통제된 실험실 환경에 적응시킨 후 1주일간 복령약침액(125mg/kg 복령약침군 및 250mg/kg 복령약침군)을 좌우 신수($BL_{23}$)에 교대로 각각 피하에 약침하고 streptozotocin을 복강내 주사하여 3일 후 diabetes mellitus 유도 정도를 평가하고 2주일간 추가 치료를 진행 한 뒤, 혈액지표(plasma glucose, insulin, TG, TC, NEFA, sGOT, sGPT, ALP, BUN, CRE)와 췌장조직의 형태학적 분석 및 염증 관련 단백질의 발현을 평가하였다. 결과 : 복령약침군(125mg/kg 복령약침군 및 250mg/kg 복령약침군)에서 insulin과 triglyceride, NEFA 수치가 유의하게 감소하였으며 간 기능 효소수치인 sGOT가 감소하는 경향을 나타내었으나, 신장기능지수는 유의한 감소를 나타내지 않았다. 특히 250mg/kg 복령약침군에서 streptozotocin 투여로 인한 pancreatic islet의 형태학적 변성이 현저하게 개선되었다. Western blot 결과 JNK-2, P-JNK-2, P-JNK-1, ERK1/2 및 phosphorylated ERK1의 발현이 감소되었다. 결론 : 복령약침이 고인슐린혈증과 고지질질혈증을 개선시키고 streptozotocin에 의한 pancreatic islet의 파괴를 억제하며, 이는 inflammation-related transcription factor인 NF-kB와도 관련이 있는 것으로 판단된다. 향후 복령약침의 항당뇨 효과와 그 기전에 관한 추가 연구가 필요할 것으로 사료된다