• 약학회지
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• 제42권4호
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• pp.408-413
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• 1998

To establish prediabetes in vitro/ model concerning the etiology of Insulin Dependent Diabetes Mellitus (IDDM) in cellular level we have designed experimental prediabefic model in pancreatic beta cells. RINm5F, HIT-T15 and isolated rat islets were chosen as pancreatic beta cells. Since interleukin-$1{\beta}$-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of IDDM, we used inteleukin-$1{\beta}$ as diabetogenic agent. For establishment of prediabetic in vitro model, the degree of beta cell deterioration was determined by cell proliferation, insulin release and morphological appearance. Cell proliferation, insulin release and morphology were changed dose-dependently in condition that inteleuldn-$1{\beta}$ was exposured to pancreatic beta cells. The concentration and exposure time of interleukin-$1{\beta}$ to set up prediabetic model in beta cell lines and isolated rat islets were 100${\sim}$1000U/ml, 48hr. And 25${\sim}$100U/ml, 48hr, respectively.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 춘계학술대회
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• pp.121-121
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• 2019

In Islamic dietary guidelines, Halal foods are allowed as edible blessed food. Most foods were categorized within halal for Muslims. The main point of Halal food is that foods are clean in every process and based on Halal standard which might be different in each country. Most pancreatic ${\beta}$ cells synthetize, store, and release insulin. Specific molecular, functional as well as ultrastructural traits of pancreatic ${\beta}$ cells could control their insulin secretion properties and survival phentoype. Insulin-secreting pancreatic ${\beta}$-cells are essential regulators of mammalian metabolism. In addition, the pancreatic ${\beta}$ cell plays an important role in the pathogenesis of type 1 and type 2 diabetes as improving glucose homeostasis by preserving, expanding and improving the function of this key cell type. However, the pharmacological effect of halal food has not been unclear yet, especially food habit-dependent diabetes. The aim of the this study was to determine the preventive effect of Iran plants extract (Almond, Garlic, Cumin, Ginkgo biloba, Holy basil, Psyllium, Satureja khuzistanica, Fenugreek, Green tea, Ipomoea betatas, Blueberry) on RINm5F cells and MIN6 cells as pancreatic ${\beta}$ cell line. The cytotoxicity of the extracts of Iran plants on RINm5F cells and MIN6 cells were measured by using MTT assays. The preventive effects of Iran plant extracts were measured by WST-8 cell proliferation assay on streptozotocin (STZ)-induced cell death in MIN6 cells. In presented result showed that all extract of Iran plants (0.01-10mg/ml) did not show cytotoxicity in RINm5F cells and MIN6 cells. Among non-cytotoxic extract, the protective effects could be detect in high dose concentration. These results suggest that the extract of Iran plants may serve as a potential therapy for diabetes.

• 생약학회지
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• 제39권4호
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• pp.335-340
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• 2008

Diabetes mellitus is metabolic disorder characterized by hyperglycemia caused by insufficient insulin secretion or insulin receptor insensitivity to endogenous insulin. It is well-known that hyperglycemia is one of the main causes of oxidative stress in both type 1 and 2 diabetes. Oxidative stress is related by death of pancreatic ${\beta}$ cell and dysfunction of ${\beta}$ cell. Although ${\beta}$ cell death or dysfunction is induced by many substances or molecules, increased evidences that oxidative stress plays a crucial role in ${\beta}$ cell death or dysfunction. Considering the importance of oxidative stress in the pathogenesis of diabetes mellitus, we investigated the cytoprotective effects against hydrogen peroxide-induced oxidative stress in pancreatic ${\beta}$ cell line RIN-m5F cell. 110 Plant sources were collected in Mt. Baek-du, and extracted with methanol. These extracts had been screened the protective effects against hydrogen peroxide-induced oxidative damage in RIN-m5F cells at 50 and 200 ${\mu}g$/ml. Of these, ten methanolic extracts, aerial part of Erigenron cannadensis, aerial part of Lespedeza juncea, whole plant of Alopecurus aequalis, fruit of Lycium chinense, leaf of Morus alba, rhizome of Polygonatum odoratum, root of Ampelosis japonica, whole plant of Ranunculus japonicus, aerial part of Polygonum sieboldii, rhizome of Arisaema amurense var. violaceum showed significant protective effects against hydrogen peroxide-induced oxidative damage in pancreatic ${\beta}$ cell line RIN-m5F cell.

• 한국식품영양과학회지
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• 제36권2호
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• pp.186-193
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• 2007

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic $\beta-cell$ mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic $\beta-cell$ mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic $\beta-cell$ mass, indicating the increased possibility of diabetic prevalence and progression. MF increased $\beta-cell$ mass by stimulating $\beta-cell$ proliferation and neogenesis and reducing $\beta-cell$ apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.463-468
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• 2012

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic ${\beta}$-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic ${\beta}$-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic ${\beta}$-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic ${\beta}$-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic ${\beta}$ cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.284-289
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• 2013

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice.

• Molecules and Cells
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• 제40권7호
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• pp.457-465
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• 2017

Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic ${\beta}$-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic ${\beta}$-cell apoptosis via an ER stress-dependent signaling pathway. STZ-induced diabetic WT and CHOP deficient mice were i.p. injected every 2 days for 6 days under BIX02189 (a specific ERK5 inhibitor) treatment in order to evaluate the role of ERK5. Hyperglycemia was exacerbated by co-treating C57BL/6J mice with STZ and BIX02189 as compared with mice administered with STZ alone. In addition, immunoblotting data revealed that ERK5 inhibition activated the unfolded protein response pathway accompanying apoptotic events, such as, PARP-1 and caspase-3 cleavage. Interestingly, ERK5 inhibition-induced exacerbation of pancreatic ${\beta}$-cell apoptosis was inhibited in CHOP deficient mice. Moreover, transduction of adenovirus encoding an active mutant form of $MEK5{\alpha}$, an upstream kinase of ERK5, inhibited STZ-induced unfolded protein responses and ${\beta}$-cell apoptosis. These results suggest that ERK5 protects against STZ-induced pancreatic ${\beta}$-cell apoptosis and hyperglycemia by interrupting the ER stress-mediated apoptotic pathway.

• Asian-Australasian Journal of Animal Sciences
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• 제16권7호
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• pp.1060-1065
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• 2003

To determine whether dietary fatty acids affect pancreatic $\beta$-cell function, the INS-1 $\beta$-cells and the pancreatic islets isolated from Zucker obese (fa/fa) rats were cultured with stearic acid and conjugated linoleic acid (CLA). As a result, DNA fragmentation laddering was substantially decreased in the INS-1 $\beta$-cells and the isolated pancreatic islets cultured with 2 mM CLA compared to those cultured with stearic acid. To investigate the mechanism by which CLA alleviates cell apoptosis under DNA fragmentation assay, we examined mRNA expressions of apoptosis-related proteins including Bax and Bcl-2 associated with cell death agonist and antagonist, respectively, in both INS-1 cells and islets cultured with 2 mM fatty acids. Bax mRNA expression was not altered by either stearic acid or CLA, whereas Bcl-2 mRNA expression was enhanced by CLA when compared to the stearic acid cultures. However, there were no changes in cell apoptosis and apoptotic-regulating gene products in either INS-1 cells or isolated islets treated with or without 2 mM CLA. It is concluded that CLA maintains $\beta$-cell viability via increased Bcl-2 expression compared to the stearic acid cultures, which may help to alleviate, at least somewhat, the onset of NIDDM in the physiological status. More detailed study is still needed to elucidate the effect of CLA on the prevention of fatty acid-induced $\beta$-cell apoptosis.

• Applied Microscopy
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• 제37권4호
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• pp.249-258
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• 2007

이자섬은 이자를 구성하는 외분비조직에 둘러싸여 존재하는 내분비세포의 집단으로, 이자섬에서 분비되는 인슐린은 $\beta$세포에서 분비되는 호르몬이며, 세포질의 리보좀에서 합성되고 골지체를 경유하여 세포질로 방출되는 기작을 가지고 있다. 충분한 양의 이자섬 이식은 인슐린 의존형 당뇨병인 제1형 당뇨병에서 정상혈당을 회복시키고, 당뇨 합병증을 방지할 수 있는 치료방법으로 사용되고 있다. 하지만 당뇨병 환자에게 이식을 위한 이자섬의 양에 비해 공여자로부터 증여된 이자섬의 양은 제한적이다. 이러한 문제점은 이자섬의 증식으로 연구되고 있으나, 배양된 이자섬이 정상 조직내의 이자섬과 형태적 기능적으로 동일한 것인지에 관한 연구는 미비하였다. 따라서 본 연구에서는 분리된 이자섬과 배양된 이자섬을 구성하는 세포들의 내부구조의 변화를 주사전자현미경, 투과전자현미경을 이용하여 세포의 미세구조를 확인하고, 인슐린 항체를 이용한 $\beta$세포 내의 인슐린 분포양상을 확인하여 다음과 같은 결과를 얻었다. 분리된 이자섬의 $\beta$세포는 일반적인 핵 미토콘드리아, 세포질세망 그리고 인슐린 과립이 분포하고, 배양된 이자섬 $\beta$세포의 경우 분리된 이자섬에 비하여 일반적인 핵의 모습과 부피가 증가한 세포질과 미토콘드리아, 세포질세망 그리고 골지체의 발달이 이루어지는 것으로 관찰되었다. 인슐린 과립의 경우 분리된 이자섬에 비해 감소하며, 세포막 주위에 분포하는 것으로 관찰되었다. 배양된 이자섬에서 관찰되는 인슐린 과립 분포의 변화, 세포질세망의 증가, 골지체의 발달은 배양된 이자섬 $\beta$세포의 인슐린 생성 분비 기능의 향상과 부피의 증가가 이루어지기 위한 세포 내부의 형태적 변화가 이루어지는 것으로 추측된다.

• Nutrition Research and Practice
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• 제8권5호
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• pp.494-500
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• 2014

BACKGROUND/OBJECTIVES: This study investigated whether Padina arborescens extract (PAE) protects INS-1 pancreatic ${\beta}$ cells against glucotoxicity-induced apoptosis. MATERIALS/METHODS: Assays, including cell viability, lipid peroxidation, generation of intracellular ROS, NO production, antioxidant enzyme activity and insulin secretion, were conducted. The expressions of Bax, Bcl-2, and caspase-3 proteins in INS-1 cells were evaluated by western blot analysis, and apoptosis/necrosis induced by high glucose was determined by analysis of FITC-Annexin V/PI staining. RESULTS: Treatment with high concentrations of glucose induced INS-1 cell death, but PAE at concentrations of 25, 50 or $100{\mu}g/ml$ significantly increased cell viability. The treatment with PAE dose dependently reduced the lipid peroxidation and increased the activities of antioxidant enzymes reduced by 30 mM glucose, while intracellular ROS levels increased under conditions of 30 mM glucose. PAE treatment improved the secretory responsiveness following stimulation with glucose. The results also demonstrated that glucotoxicity-induced apoptosis is associated with modulation of the Bax/Bcl-2 ratio. When INS-1 cells were stained with Annexin V/PI, we found that PAE reduced apoptosis by glucotoxicity. CONCLUSIONS: In conclusion, the present study indicates that PAE protects against high glucose-induced apoptosis in pancreatic ${\beta}$ cells by reducing oxidative stress.