• Experimental and Molecular Medicine
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• 제51권2호
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• pp.9.1-9.10
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• 2019

Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of ${\alpha}-SMA^+/PCNA^+$ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of $p27^{Kip1}$ was decreased. The expression of $Kr{\ddot{u}}ppel$-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.

• 대한한방내과학회지
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• 제43권4호
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• pp.606-624
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• 2022

Objective: The aim of this study was to compare the effects of different doses of Geumnyeonyijin-tang (GNYJT) water extracts with those of metformin (250 mg/kg) in mild diabetic-obese mice. Methods and Results: The 48 mice were divided into 1 normal pellet diet (NFD) group and 5 high-fat diet (HFD) groups. At the end of 12 weeks of oral administration of metformin (250 mg/kg) or GNYJT water extracts (400, 200, or100 mg/kg), the effects were evaluated. The HFD control mice showed noticeable increases in body weight, adipose tissue density, fat pad weight of the periovarian and abdominal wall, and insulin, blood glucose, and HbA1c levels, with decreases in serum HDL levels. Increases in the periovarian and dorsal abdominal fat pad, regions of steatohepatitis, adipocyte hypertrophy, and hepatocyte hypertrophy were also discovered. The HFD group showed a decline in glucose levels and elevation of hepatic gluconeogenesis, suggesting an HFD-induced AMPK downregulation related to glucose dysregulation, as well as lipid metabolism related to obese insulin-resistant type II diabetes, dyslipidemia, and oxidative stress related diabetic hepatopathy (non-alcoholic fatty liver disease, NAFLD). Conclusion: Assessment of the key parameters for inhibition of diabetes and related complications in HFD-fed diabetic-obese mice demonstrated that GNYJT water extracts have favorable ameliorating effects. The effect of GNYJT was manifested through the stimulation of AMPK upregulation of related hepatic glucose enzyme activities and expression of lipid metabolism-related genes. Therefore, appropriate oral dosages of GNYJT could be promising as a new preventive candidate for controlling diabetes and related complications. Further screening of biologically active compounds, elucidation of detailed mechanisms, and more animal studies are warranted.

• Archives of Pharmacal Research
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• 제29권9호
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• pp.786-794
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• 2006

We observed the suppressive effect of a powder formulation of African black tea extract prepared from the leaves of Camellia sinensis on type 2 non-insulin dependent diabetic mice, $KK-A^y/TaJcl$. Black tea extract significantly showed suppressive effect of the elevation of blood glucose on oral glucose tolerance test of 8 week-old $KK-A^y/TaJcl$ mice (p<0.05). Long-term treatment with black tea extract showed significant suppression of post-prandial blood glucose and obesity (p<0.05). The weight of the intestine of mice treated with black tea extract was significantly reduced (p<0.05). From these results, African black tea used in this study showed a suppressive effect on the elevation of blood glucose during food intake and the body weight.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.132.2-133
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• 2003

The biological effects of NADPH-dependent isocitrate dehydrogenase (IDPc) inhibitor, DA-11004, was investigated in obese diabetic (ob/ ob) mice. DA-11004, metformin, and oxalomalate were daily injected (ip) for 8 weeks and after completing an 8-week period of experiment, mice were sacrificed at 1 hr after the last drugs treatment to collect their blood, liver, and adipose tissues(epididymal and retroperitoneal fat). (omitted)

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.223-229
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• 2019

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic $BKS.Cg-m+/+Lepr^{db}$ mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.

• 대한수의학회지
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• 제29권4호
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• pp.549-558
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• 1989

This experiment was carried out to investigate the influence of Aloe vera in the pancreatic islets of streptozotocin diabetic mice. Experimental diabetes was induced in ICR mice with a single injection of SZ(140mg/kg body weight, ip). The mice demonstrating hyperglycemia 48 hours after SZ injection were treated for 16 days with Aloe vera(300, 800mg/kg). Plasma glucose was measured, and for morphological studies of the islets specimens were stained with hematoxylin-eosin and by immunocytochemical methods. Then we observed the morphological changes of islets. Polymorphonuclear cells were infiltrated at the periphery of the islets 48 hours after SZ injection in SZ-treated ICR mice, but no prominent WBC infiltration was observed throughout the experiment. Blood glucose in mice treated with Aloe vera after SZ injection was higher than that of SZ injected mice, and mononuclear cells were heavily infiltrated at the islets 16 days after Aloe vera treatment(300mg/kg), and significant islets infiltration of mononuclear cells was observed 30 days after Aloe vera treatment(800mg/kg). Islets of ICR mice treated with Aloe vera after SZ injection showed severer insulitis, degranulation and necrosis of B cells than those of SZ injected mice. These studies indicate that Aloe vera in SZ injected mice increases vascular permeability and number of WBC in pancreatic islets, and potentiates destruction of B cells by cell-mediated immune system.

• Nutrition Research and Practice
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• 제10권1호
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• pp.42-48
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• 2016

BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-$1{\beta}$ and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells.

• 한국잠사학회:학술대회논문집
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• 한국잠사학회 2002년도 Join Meetings of Korean Society of Sericultural Science and Japanse Society of Sericultural Science
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• pp.126-126
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• 2002

No Abstract, See Full Text

• 생명과학회지
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• 제20권7호
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• pp.1012-1018
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• 2010

본 연구에서, 고지방식이에 의한 비만, streptozotocin처리에 의한 당뇨 및 노화에 의해 알츠하이머병의 원인 유전자인 APP의 발현이상이 생기는지를 조사하였다. 일반식이(ND)/고지방식이(HFD), 16주령/26주령, 및 정상/당뇨 등의 조건별 8가지 조합에 88마리의 C57BL/6 생쥐를 각 그룹에 최소 10마리씩 나누어 키웠으며, 각 실험생쥐로부터 추출한 부고피하지방 및 부고환지방조직에서의 APP mRNA 발현양을 quantitative real-time PCR로 측정하였다. 그 결과, 피하지방조직에서의 APP 유전자는 16주령과 26주령에서 고지방식이로 키워 비만을 유도한 동물에서 2배정도 높게 발현되었으나(16주령 $125.0{\pm}13.9$ vs. $63.5{\pm}9.9$, p=0.001; 26주령 $120.2{\pm}6.0$ vs. $51.8{\pm}6.3$, p<0.0001), 부고환지방조직에서는 APP 발현양의 차이가 나타나지 않았다. 16주령과 26주령 사이에서의 노화에 따른 APP 발현양의 차이도 나타나지 않았다. 또한, 일반 및 고지방식이로 키운 16주령 생쥐의 피하지방조직 APP 유전자 발현은 STZ에 의해 유도된 당뇨병 생쥐에서 크게 감소되었다(ND non-diabetic $63.5{\pm}9.9$ vs. diabetic $40.2{\pm}5.0$, p<0.05; HFD $125.0{\pm}13.9$ vs. $67.0{\pm}9.0$, p<0.01). APP mRNA 발현양의 선형회귀분석에 의하면, 당뇨병이 유발되지 않은 일반 생쥐(R=0.657, p<0.0001, n=39)와 당뇨병 생쥐(R=0.508, p=<0.0001, n=49) 모두에서의 APP mRNA 발현양이 체중과 깊은 연관성이 있음이 확인되었으나, APP mRNA 양과 혈당과의 연관성은 나타나지 않았다. 이는 STZ에 의한 당뇨병 생쥐에서 관찰된 APP mRNA 발현의 감소는 고혈당증에 의한 것이 아닌 체중감소의 영향인 것으로 추측된다. 본 연구의 결과로 APP mRNA는 생쥐의 피하지방 및 부고환지방에서 발현되고 있고, 비만에의 의해 증가하며, 체중감소에 의해 감소한다는 것을 확인하였다. 이들 결과는 사람에게서 확인된 체중변화에 의한 APP 이상발현 현상을 더욱 분명히 보여주었으며, 이런 APP 이상발현이 중년기 비만과 노령기의 알츠하이머병 환자 뇌에서의 amyloidogenesis 증가 매개자로서의 역할 가능성을 시사한다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2007년도 추계 학술대회
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.