• Title/Summary/Keyword: $\beta-cell$ function

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Decreased Expression of Phospholipase C-$\beta$2 in Human Platelets with Impaired Function

  • Lee, Sang-Bong;A. Koneti Rao;Lee, Kweon-Haeng;Xu Yang;Bae, Yun-Soo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.11a
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    • pp.75-84
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    • 1996
  • Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate (IP$_3$), mobilization of intracellular Ca$\^$2+/, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation. A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, seven, out often known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC-${\gamma}$2 > PLC-${\beta}$2 > PLC-${\beta}$3 > PLC-${\beta}$l > PLC-${\gamma}$ > PLC-$\delta$1 > PLC-${\beta}$4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-${\beta}$2, whereas PLC-${\beta}$4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-${\beta}$2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.

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Dexamethasone Inhibits the Formation of Multinucleated Osteoclasts via Down-regulation of ${\beta}_3$ Integrin Expression

  • Kim, Yong-Hee;Jun, Ji-Hae;Woo, Kyung-Mi;Ryoo, Hyun-Mo;Kim, Gwan-Shik;Baek, Jeong-Hwa
    • Archives of Pharmacal Research
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    • v.29 no.8
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    • pp.691-698
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    • 2006
  • Although glucocorticoids are known to affect osteoclast differentiation and function, there have been conflicting reports about the effect of glucocorticoids on osteoclast formation, leading to the assumption that microenvironment and cell type influence their action. We explored the effect of the synthetic glucocorticoid analog dexamethasone on the formation of osteoclasts. Dexamethasone inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts without affecting the formation of TRAP-positive mononuclear cells in a coculture of mouse osteoblasts and bone marrow cells. Dexamethasone did not inhibit mRNA expression levels of the receptor activator of nuclear factor-kB ligand and osteoprotegerin, the essential regulators of osteoclastogenesis. Dexamethasone down-regulated the expression of ${\beta}_3$ integrin mRNA and protein but did not alter expression of other osteoclast differentiation marker genes. Both dexamethasone and echistatin, a ${\beta}_3$ integrin function blocker, inhibited TRAP-positive multinucleated osteoclast formation but not TRAP-positive mononuclear cell formation. These results suggest that dexamethasone inhibits the formation of multinucleated osteoclasts, at least in part, through the down-regulation of ${\beta}_3$ integrin, which plays an important role in the formation of multinucleated osteoclasts.

Antioxidant effect of myricetin with other antioxidants, taurine and $\beta$-carotene on mouse melanoma cell

  • Yu, Ji-Sun;Kim, An-Keun
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.69-69
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    • 2003
  • There are now increasing evidences that free radicals and reactive oxygen species are involved in a variety of pathological events. Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS lead to lipid peroxidation, massive protein oxdiation and degradation. Under normal conditions, antioxidant are substnaces that either directly or indirectly protect cell against adverse effect of ROS. several biologically important compound include ${\beta}$-carotene, taruine and flavonoids reported have antioxidant function. The various antioxidant either scavange superoxide and free radicals or stimulate the detoxification mechanisms within cells resulting in increased detoxification of free radicals formation and thus in prevention of many pathophysiologic processes. This study carried out to investigate the antioxidant activity of flavonoids, myricetin with other antioxidants, ${\beta}$-carotene and taurine on B16Fl0. In order to investigate the efficacy of antioxidant activity, we measured cell viability, antioxidant enzyme activity (SOD, GPX, CAT) and intracellular reactive oxygen intermediate (ROI). In this results, we show that these flavonoids with other antioxidant substrates are increased antioxidant activity level.

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Acetylcholinesterase Inhibitory Activity and Protective Effect against Cytotoxicity of Perilla Seed Methanol Extract (들깨 메탄올 추출물의 acetylcholinesterase 억제활성 및 세포독성 보호효과)

  • Choi, Won-Hee;Um, Min-Young;Ahn, Ji-Yun;Kim, Sung-Ran;Kang, Myung-Hwa;Ha, Tae-Youl
    • Korean Journal of Food Science and Technology
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    • v.36 no.6
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    • pp.1026-1031
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    • 2004
  • Acetylcholinesterase inhibitory activity and protective effect against cytotoxicity of PC 12 cell induced by beta-amyloid protein and glutamate were examined in perilla seed methanol extract and its solvent fractions. Methanol extract of perilla seed showed dose-dependent acetylcholinesterase inhibitory activity, with n-butanol fraction showing strongest activity. Perilla seed methanol extract also decreased glutamate- and ${\beta}-amyloid$ protein $(A{\beta})-induced$ cytotoxicities of PC 12 cells dose-dependently. Formation of TBARS induced by $FeSO_{4^-}H_2O_2$ in rat brain was significantly reduced by perilla seed methanol extract, with strongest protective activity formation of TBARS shown in n-butanol fraction. Results suggest perilla seed methanol extract may attenuate actylcholinesterase activity and cytotoxicity induced by glutamate and ${\beta}-amyloid$ protein through suppression of oxidative stress.

Relationship between Visceral Adiposity Index, Insulin Resistance and Pancreatic Beta Cell Function According to the Prevalence of Metabolic Syndrome in Korean Obese Adults (한국 비만성인의 대사증후군 유병에 따른 내장지방지수와 인슐린저항성, 췌장 베타세포기능과의 관련성)

  • Shin, Kyung-A
    • 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.

Moderate diet-induced weight loss is associated with improved insulin sensitivity in middle-aged healthy obese Korean women

  • Lee, Hye-Ok;Yim, Jung-Eun;Kim, Young-Seol;Choue, Ryowon
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.469-475
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    • 2014
  • BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the effects of moderate caloric restriction on ${\beta}$-cell function and insulin sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven obese pre-menopausal Korean women participated in a 12-week calorie restriction program. Data on total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and anthropometrics were collected. A dietary intake assessment was based on three days of food recording. Additionally, ${\beta}$-cell function [homeostasis model assessment of ${\beta}$-cell (HOMA-${\beta}$), insulinogenic index (ISI), C-peptide:glucose ratio, and area under curve insulin/glucose ($AUC_{ins/glu}$)] and insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded. RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks, BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased significantly (P < 0.05). After calorie restriction, weight, body fat percentage, hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at fasting and 120 min, $AUC_{glu}$ and the insulin area under the curve all decreased significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS: Moderate weight loss due to caloric restriction with reduction in insulin resistance improves glucose tolerance and insulin sensitivity in middle-aged obese women and thereby may help prevent the development of type 2 diabetes mellitus.

Effects of Inhibitors on the Function and Activity of Topoisomerase, and Gene Expression in HL-60 Human Leukemia Cells (HL-60 세포의 유전자 발현 및 topoisomerase의 기능 활성에 미치는 억제제의 영향)

  • Jeong, In-Cheol;Cho, Moo-Youn;Park, Jang-Su
    • Journal of Life Science
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    • v.18 no.1
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    • pp.75-83
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    • 2008
  • This studies were designed to elucidate whether inhibitors of topoisomerase regulate function and activity of topoisomerase, and gene expression in HL-60 human leukemia cells. HL-60 cells were treated with 10-hydroxycamptothecin or doxorubicin, total RNA was isolated, and expressed genes were investigated with human oligonucleotide microarray containing 10K gene, respectively. Expression profiles of the human leukemia HL-60 cells treated with 10-hydroxycamptothecin (10-CIT) or doxorubicin associated with signal transduction,. cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription and immune response, especially genes related with transcription and cell growth. In HL-60 cells treated with 10-CPT, the expression of topoisomerase III${\alpha}$, III${\beta}$ and I gene from oligo chip microarray analysis were increased over, but the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were decreased over. In contrast, the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were increased over in HL-60 cells treated with doxorubicin, whereas the expression of topoisomerase III${\alpha}$ and III${\beta}$ mRNA remained no significant change. These results suggest that these data may be useful for novel therapeutic markers.

The Effect of Dietary Fat on Insulin Secretion and Pancreatic β-Cell Mass in 90% Pancreatectomized Diabetic Rats (식이 지방이 췌장 90%를 제거한 당뇨 흰쥐의 인슐린 분비능과 췌장 베타세포의 양에 미치는 영향)

  • Park, Sun-Min;Park, Chun-Hee;Hong, Sang-Mee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.2
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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 protective effect of Halal food extract in pancreatic beta cell lines.

  • Kim, Seong-sun;Jin, Yu-Mi;Song, Young-Jae;AYE, AYE;Soh, Ju-Ryoun;Jeon, Yong-Deok;Jin, Jong-Sik
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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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.

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Endocrinic Effects of Toxaphene and Chlordane in Human Hepatoma Cell (HepG2 Cell) Transfected with Estrogen Receptor and Luciferase Reporter Gene (에스트로겐 수용체 및 Luciferase 리포터 유전자 도입 사람 간 종양세포(HepG2 Cell)에서 Toxaphene과 Chlordane의 내분비 독성)

  • Kim Kyeong-Bae;Jung Ji-Won;Yang Se-Ran;Kang Kyung-Sun;Lee Yong-Soon
    • Toxicological Research
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    • v.20 no.3
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    • pp.205-211
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    • 2004
  • Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.