• 한국식품영양학회지
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• 제25권1호
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• pp.123-131
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• 2012

The objective of the present study was to evaluate the potential antidiabetic and antioxidant effect of the ethanol extract from Chrysanthemum cornarium L. var. spatiosum(CSE) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. In this study, the antidiabetic effect of CSE was examined using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide(MTT) cell proliferation assay, lactate dehydrogenase(LDH) release assay, $NAD^+$/NADH ratio and insulin secretion. To further investigate whether CSE is involved in the antioxidant activity of alloxan-damaged HIT-T15 cells, its antioxidant effect against alloxan-induced oxidative stress was measured in HIT-T15 cells by determining the levels of 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, CSE significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular NAD+/NADH ratio and insulin secretion were also significantly increased by 1.7-fold and 1.3-fold, respectively, after treatment with 100 ${\mu}g/m{\ell}$ CSE. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while CSE significantly elevated the levels of antioxidant enzymes. These findings suggest that CSE could have a protective effect against cytotoxicity and dysfunction of pancreatic cells in the presence of alloxan-induced oxidative stress.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• 한국자원식물학회지
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• 제25권2호
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• pp.184-192
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• 2012

본 연구는 췌장베타세포인 HIT-T15 세포를 이용하여 매실주정추출물(PME)의 alloxan에 의한 산화스트레스로부터의 세포보호, 인슐린 분비능 및 항산화 효소 활성을 평가하였다. PME는 alloxan에 의해 유발된 산화스트레스로부터 세포를 보호하여 세포생존율을 증가시켰다. PME는 세포막 손상지표인 LDH 방출을 억제하였고 $NAD^+$/NADH ratio를 유의적으로 증가시켜 세포사멸이 억제되어짐을 확인하였다. 또한 alloxan 단독처리군에 비해 250 ${\mu}g$/ml PME 처리군에서 인슐린 분비량이 유의성 있게 증가하였다. Alloxan과 PME를 동시에 처리하여 HIT-T15세포의 항산화효소 활성을 측정했을 때 산화스트레스에 의해 감소되었던 항산화효소 활성이 PME에 의해 보호되는 효과를 확인하였다. 이상의 연구결과로부터 PME는 세포괴사 및 DNA fragmentation을 억제하고 세포내 항산화효소 활성을 증가시켜 alloxan에 의해 유발된 산화스트레스로부터 췌장베타세포를 보호하고 이에 따른 인슐린 분비능 조절 효과가 있는 것으로 생각된다.

• 동의생리병리학회지
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• 제28권5호
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• pp.486-493
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• 2014

Adipocytes are endocrine cells that release bioactive mediators called adipokines. In condition of obesity characterized by low-grade chronic inflammation, adipocytes release inflammatory adipokines, which is related to insulin resistance. Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on in Korean medicine. BJCST is also expected to have anti-obesity activities. In the present study, we examined whether BJCST modulate the production of inflammatory adipokines and the activations of the mitogen-activated protein kinases (MAPK) signaling pathway related to induce adipocyte inflammation to elucidate the effects and its mechanism of BJCST on lowering the content of inflammatory adipokines in 3T3-L1 adipocytes. As a result, BJCST suppressed the production of proinflammatory cytokines, tumor necrosis factor (TNF) $-{\alpha}$, interleukin (IL) $-1{\beta}$, IL-6, interferon (IFN) -${\gamma}$, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and the production of other inflammatory mediators, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO)viadownregulationofcyclooxygenase-2(COX-2)andinducible NO synthase (iNOS) gene expressions. In addition, BJCST decreased the phosphorylation of MAPK that promotes the production of inflammatory adipokines in 3T3-L1 mature adipocytes. In conclusion, BJCST could regulate the production of inflammatory adipokines and MAPK signaling pathway related to induction of adipose inflammation.

• Asian-Australasian Journal of Animal Sciences
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• 제20권7호
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• pp.1156-1168
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• 2007

The somatotropic (GH-IGF-I) axis consists of many hormonal and nutritional factors that control GH release from the somatotrophs in the anterior pituitary. The GH-releasing substances are GHRH and GHS (GHRP or ghrelin), while the GH release-inhibiting substances are somatostatin (SRIF), insulin-like growth factor-I (IGF-I), leptin and glucocorticoids. However, there is evidence showing that nutrition is involved in the control of the somatotropic axis. In addition, weaning is a drastic event for neonates because their alimentary and endocrine circumstances are changed due to the switch, even if gradual, from a liquid milk diet to one composed of such solids as hay and grains. The biological role of ghrelin is one of the hormonal factors that have been focused on ever since ghrelin was discovered at the end of the last century. A 27-amino acid peptide that is mainly synthesized and released from the abomasum epithelium, ghrelin has not been fully evaluated in relation to the somatotropic axis of the ruminant. It has also proven difficult even to investigate the cellular mechanisms of ghrelin action, because this hormone exerts animal-species-dependent actions via a complex set of intracellular signaling pathways. This is also the case for the action of leptin. Another substance, IGF-I, shows a partial inhibitory action on GH secretion in the ruminant. The effect of nutrition is also different among animal species. This is evident by the fact that undernutrition suppresses the circulating GH levels in rodents, but increases it in ruminants and humans. Recently, weaning has been shown to change the postprandial GH responses in ruminants; milk feeding increases, but hay and concentrate feeding suppress, the postprandial circulating GH levels. Even if the postprandial GH level is increased, the ghrelin level is decreased by milk feeding. Macronutrients also possess stimulatory and inhibitory actions on GH secretion in vivo and in vitro. These findings indicate the complexity of the control mechanisms of the somatotropic axis. In the present review, we summarize recent findings on the factors controlling the axis of the ruminant.

• 한국식품영양과학회지
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• 제13권4호
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• pp.437-443
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• 1984

포도당으로 perfusion한 쥐의 뒷다리 근육에 전기자극으로 근육운동을 유도하여 대사물의 농도변화를 측정한 결과는 아래와 같다. 근육내의 구연산회로대사물, 피루빅산, 젖산등의 농도가 상당히 증가하였고 알라닌, 글루타믹산, 아스파틱산등의 아미노산은 약간 증가하였고, 크레아틴 포스페이트, ATP의 농도가 급강하 한데 반하여 AMP와 암모니아의 농도가 증가하였다. 이 결과는 운동시에 에너지대사를 촉진시키는 구연산회로 대사물 일부는 아미노산으로부터 transamination 반응을 통하여 공급되고, 일부는 purine nucleotidecycle반응을 통하여 아스파틱산으로 공급되고 있음을 밝혔다.

• Nutrition Research and Practice
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• 제17권1호
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.141-149
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• 2007

Madhuca indica has been used ethnomedically in Indian folks. In the present study we have investigated anti-inflammatory, anti-ulcer and hypoglycaemic effect of ethanolic extract (EE) and crude alkaloid extract of Madhuca indica seed cake on albino rats. The study showed that the EE had a significant, dose dependent anti-edematogenic, anti-ulcerogenic and hypoglycaemic activity, whereas the crude alkaloid extract exhibited a significant only. Both the extracts possess dose dependent inhibitory activity on carrageenan-induced edema, inhibiting prostaglandins or mediators involved in prostaglandin synthesis, the second phase of inflammation. The EE was significantly effective in protecting pylorus-ligation-induced gastric ulcers at a higher dose level. The active principle of EE seems to be a selective inhibitor of the COX II (prostaglandin synthesis) without important effect on COX I since, EE exhibited both anti-edematogenic and anti-ulcerogenic effect. The EE was effective in reducing the plasma glucose level in normal albino rats in a dose dependent manner, producing hypoglycaemic effect by stimulating the release of insulin from the ${\beta}-cells$ and/or increasing the uptake of glucose from the plasma.

• 약학회지
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• 제34권6호
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• pp.439-446
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• 1990

The general pharmacological actions of recombinant human growth hormone (rHGH) were investigated. It had hypothermic action but neither sedative nor analgesic action. No pharmacological effects were observed in isolated guinea pig ileum and tracheal muscle and rat fundus and uterus. Slight hypotensive action with no effect on respiration was revealed at a dose of 20 IU/kg i.v. of rHGH in rabbits. The rHGH exhibited a weak inhibitory action of glucose tolerance in normal rats, significantly lowered the blood glucose contents in adrenalectomized rats 20 min after i.v. administration (80IU/kg), and produced a significant inhibitory effect on in vitro glycerol release in epinephrine-stimulated epididymal fat pad segments of rats.

• 대한핵의학회지
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• 제3권2호
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• pp.23-27
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• 1969

Plasma glucose levels before and after oral glucose administration have been compared in a group of 76 thyrotoxic subjects and a group of 8 normal control subjects in order to study the effect of glucose loading in thyrotoxicosis. Following were the results: 1. The mean fasting plasma glucose level was elevated in the thyrotoxic group(95.5mg%) compared to normal control group (88mg%). 2. The peak of glucose tolerance curve is at 30 minutes after glucose administration in both groups, but its mean value was 44mg% higher in thyrotoxic group than in control group. 3. The plasma glucose levels returned towards the fasting level in the later stage of the test more rapidly in thyrotoxic group than in control group. 4. 69.6% of oral glucose tolerance tests were impaired in the thyrotoxic group, and the occurance of abnormal glucose tolerance could be related to the degree of thyrotoxicity, sex and age. 5. The mechanisms of the impaired glucose tolerance in thyrotoxicosis are thought to be related to an increased rate of glucose absorption from gastrointestinal tract, abnormal liver function with decreased hepatic glycogenesis, increased glucose oxidation, decreased pancreatic release of insulin, and genetic relationship between diabetes and thyrotoxicosis.