• Title/Summary/Keyword: diabetic rats

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The role of discoid domain receptor 1 on renal tubular epithelial pyroptosis in diabetic nephropathy

  • Zhao, Weichen;He, Chunyuan;Jiang, Junjie;Zhao, Zongbiao;Yuan, Hongzhong;Wang, Facai;Shen, Bingxiang
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.427-438
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    • 2022
  • Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 after Administration of Endotoxin in Diabetic Rats (내독소로 자극된 당뇨 쥐에서 단백분해효소와 그 억제제 발현)

  • Seo, Ki Hyun;Choi, Jae Sung;Na, Joo Ok;Uh, Soo Taek;Kim, Yong Hoon;Park, Choon Sik
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.3
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    • pp.256-264
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    • 2006
  • Background: An acute lung injury(ALI) is characterized by the recruitment, activation, and apoptosis of inflammatory cells, numerous products released by inflammatory cells such as reactive oxygen species, inflammatory mediators, and a variety of proteolytic enzymes. It was reported that bacterial infections in diabetics showed impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflamed tissue. However, the effect of the proteinase - inhibitor (MMP-9 vs TIMP-1) in ALI in diabetics is unclear. This study evaluated the differences in the expression of MMP-9 and TIMP-1 after the stimulation of endotoxin in a rat model. Methods: Six-week-old male Sprague-Dawley rats were classified into normal, DM, LPS and DM+LPS groups. The peripheral blood, BAL fluids, and lung tissues were obtained from individual rats. The MMP-9 activity was measured by gelatin zymography and the TIMP-1 level was measured by Western blotting. Results: The total BAL cells of the DM-LPS groups were significantly lower than the LPS groups (p < 0.01). The MMP-9 activities in the serum were higher in the DM+LPS groups than in the other groups. The MMP-9 activities in the BAL fluids were significantly higher in the DM+LPS group than in the normal and diabetic rats (p < 0.05). TIMP-1 expressions in the BAL fluids were significantly lower in the DM+LPS group than other groups (p < 0.05). The ratio between MMP-9 and TIMP-1 in the BAL fluids was significantly higher in the DM+LPS groups (p < 0.05). Conclusion: In ALI in diabetics the higher MMP-9 activity and lower TIMP-1 level are believed to prolonged and intensify the course of inflammation.

Determination of Total Chiro-inositol Content in Selected Natural Materials and Evaluation of the Antihyperglycemic Effect of Pinitol Isolated from Soybean and Carob

  • Kim, Jung-In;Kim, Jae-Cherl;Joo, Hee-Jeong;Jung, Suk-Hee;Kim, Jong-Jin
    • Food Science and Biotechnology
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    • v.14 no.4
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    • pp.441-445
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    • 2005
  • Pinitol and chiro-inositol exert insulin-like effect by mediating post-receptor signaling pathway. Total chiro-inositol concentrations, including pinitol, chiro-inositol, and their derivatives, were determined in 115 natural and food materials to identify economical sources for mass production of pinitol. Carob pod, Bougainvillea, soy whey, and soybean oligosaccharides were rich sources of chiro-inositol. Pinitol was isolated from soy whey and carob pod, considered as economically viable sources, by chromatographic separation using activated carbon. Soy and carob pinitols had same chemical structure as that of reference pinitol based on HPLC and NMR results. Oral administration of soy pinitol and carob pinitol (10 mg/kg) significantly decreased blood glucose at 2-6 hr in streptozotocin-induced diabetic rats. These results suggest pinitol isolated from soy whey and carob pod could be beneficial in controlling blood glucose in animal model of diabetes mellitus.

Phytochemical and Pharmacological Investigations on Moringa peregrina (Forssk) Fiori

  • Elbatran, Seham A.;Abdel-Salam, Omar M.;Abdelshfeek, Khaled A.;Nazif, Naglaa M.;Ismail, Shams I.;Hammouda, Faiza M.
    • Natural Product Sciences
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    • v.11 no.4
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    • pp.199-206
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    • 2005
  • Investigation of M. peregrina aerial parts revealed the isolation and identification of 4-flavonoidal compounds, quercetin, quercetin-3-0-rutinoside (rutin), chrysoeriol-7-0-rhamnoside 6,8,3',5'-tetramethoxy apigenin. The compounds were identified by TLC, PC, MS, and $H^1-NMR$. The fatty acids and unsaponifiable matter were studied. The $LD_{50}$ for M. peregrina was 113.4 mg/100g b.wt. Repeated intraperitoneal injection of 1/20 and 1/10 $LD_{50}$ (5.67 mg and 11.34 mg/100g b.wt.) of defatted alcoholic of M. peregrina for 30 days induced significant decrease in serum glucose, liver enzymes and lipid components. M. peregrina administered i.p., 30min prior to carrageenan at the above doses significantly inhibited the rat paw oedema response, In acute pain models, namely, the acetic acid-induced writing and hot-plate assay, M. peregrina exhibited marked analgesic properties. In addition, M. peregrina administered at time of indomethacin injection inhibited the development of gastric lesions in rats.

Review of Domestic Experimental Studies of Korean Medicine Treatment for Diabetes Mellitus Since 2013 (당뇨병의 한의학적 치료에 대한 국내 실험연구 고찰 - 2013년 이후)

  • Son, Ah-hyun;Koh, Ji-yoon;Lee, Dong-keun;Shin, Hyeon-su
    • The Journal of Internal Korean Medicine
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    • v.38 no.1
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    • pp.10-19
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    • 2017
  • Objective: This study reviewed experimental studies on the effects of Korean medical treatment for diabetes mellitus (DM). Method: We reviewed 24 studies about DM that had been published since 2013. We searched the Korean Institute of Oriental Medicine (KIOM) database with the keyword '당뇨', '消渴', 'Diabetes'. Results: 1. The studies used various Korean medicine treatments; 15 used single medicinal herbs, 6 used herbal complexes, and 2 used acupuncture. 2. The measurement parameters used in the studies included blood glucose, body weight, histochemical change, lipid parameters, and food/water intake. Anti-diabetic effects were demonstrated in most of the studies. 3. The experimental animals used were rats or mice. There were 15 type 1 diabetes models, 7 type 2 diabetes models, and one normal model. Among them, 13 cases of chemical diabetes induced by Streptozotosin (STZ, type 1 diabetes inducer) were the most common. Conclusion: Further articles on Korean medical treatment of DM should be studied.

The Effects of Nelumbinis Rhizomatis Nodus on Blood Glucose and Serum Lipid Levels in Streptozotocin-Induced Diabetic Rats (연근(蓮根)이 Steptozotocin으로 유발된 당뇨병(糖尿病) 백서(白鼠)의 혈당(血糖) 및 혈중(血中) 지질(脂質)에 미치는 영향)

  • Lee, Yu-Gyoung;Chai, Jung-Won
    • The Journal of Pediatrics of Korean Medicine
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    • v.22 no.2
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    • pp.141-153
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    • 2008
  • Objectives : This study was designed to investigate the effects of Nelumbinis Rhizomatis Nodus(NRN) on production levels of Blood Glucose and Serum Lipid Levels. Methods : This study is about changes of blood glucose levels, body weights, levels of food and water uptake, levels of total cholesterol in the body, triglyceride, Creatinine, and BUN production by NRN extract. Results : Treatment with NRN regulated blood glucose levels effectively, but treatment with NRN did not affect body weights, food and water uptake. In addition, treating with NRN also lowered levels of total cholesterol, which is important for diabetes, and also lowered levels of triglyceride, too. Serum Creatinine levels were not affected, but serum BUN levels were lowered by treating with NRN, which were elevated in diabetes. Conclusions : These results demonstrate that NRN is effective to treat DM level and also has anti-hyperlipidemic effect.

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Effect of Sopyung-tang Extract on Insulin Secretion and Gene Expression in RIN-m5F Cells (소평탕(消平湯)이 RIN-m5F 세포에서 인슐린 분비 및 유전자 발현에 미치는 영향)

  • Youn, Sung-Sik;Cho, Chung-Sik
    • The Journal of Internal Korean Medicine
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    • v.31 no.1
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    • pp.25-39
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    • 2010
  • Background : At high glucose levels in $\beta$-cells, cell viability and insulin secretion are decreased by glucotoxicity. Sopyung-tang(SPT) had an effect on blood glucose level decrease and antioxidant enzyme activities in streptozotocin-induced diabetic rats. Objectives : This study performed a series of experiment to verify the effects of SPT extract on the cell viability, antioxidant enzyme activities, insulin secretion and insulin mRNA expression at hyperglycemic states of RIN-m5F. Methods : After treatment at various concentrations of SPT added to the RIN-m5F cells, cell viability by MTT assay, free radical-scavenging activity, SOD activity and insulin secretion were measured. Additionally, insulin-related gene expression was measured using real-time RT-PCR. Results : Compared to the control group, SPT extract showed considerable effects on RIN-m5F cell viability, DPPH radical-scavenging activity, superoxide dismutase (SOD) activity, insulin secretion and insulin-related gene expression. Conclusions : This study showed that SPT extract has an effect on $\beta$-cell cell viability, insulin secretion and insulin-related gene expression. Thus, SPT extract may be used for treatment of diabetes and its complications. Further mechanism studies of SPT seem to be necessary on the glucotoxicity and oxidative stress.

Effect of Flavonoids from Scutellariae Radix on Cataract Formation and Polyol Accumulation in Rat Lens (황금의 Flavonoid 성분들이 Rat 수정체의 백내장 형성과 Polyol 축적에 미치는 효과)

  • Shin, Kuk-Hyun;Chae, Yun-Jung;Chung, Myung-Sook;Lee, Hee-Ju
    • Korean Journal of Pharmacognosy
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    • v.25 no.1
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    • pp.41-46
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    • 1994
  • The ether, ethylacetate and n-butanol soluble fractions from the roots of Scutellaria baicalensis showed a significant inhibition of lens aldose reductase (AR) activity in vitro. During systematic fractionation of the active fractions, 7 flavonoids were isolated and compared their inhibitory activities against rat AR using DL-glyceraldehyde as a substrate, among which baicalin (VII) was found to exhibit the most potent inhibitory activity. Baicalin (VII) and wogonin-7-O-glucuronide (VI), with repeated treatments (30 mg/kg/day, i.p.) throughout the experimental periods caused a significant suppression of cataract formation induced by galactose (40 g/kg/day) as well as the decrease of galactitol accumulation in the rat lens. The flavonoids also exhibited a significant inhibition of sorbitol accumulation in the lenses of diabetic rats induced by streptozotocin (STZ).

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Production and Its Anti-hyperglycemic Effects of γ-Aminobutyric Acid from the Wild Yeast Strain Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1

  • Han, Sang-Min;Lee, Jong-Soo
    • Mycobiology
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    • v.45 no.3
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    • pp.199-203
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    • 2017
  • This study was done to produce ${\gamma}$-aminobutyric acid (GABA) from wild yeast as well as investigate its anti-hyperglycemic effects. Among ten GABA-producing yeast strains, Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1 produced high GABA concentration of $134.4{\mu}g/mL$ and $179.2{\mu}g/mL$, respectively. P. silvicola UL6-1 showed a maximum GABA yield of $136.5{\mu}g/mL$ and $200.8{\mu}g/mL$ from S. carnicolor 402-JB-1 when they were cultured for 30 hr at $30^{\circ}C$ in yeast extract-peptone-dextrose medium. The cell-free extract from P. silvicola UL6-1 and S. carnicolor 402-JB-1 showed very high anti-hyperglycemic ${\alpha}$-glucosidase inhibitory activity of 72.3% and 69.9%, respectively. Additionally, their cell-free extract-containing GABA showed the anti-hyperglycemic effect in streptozotocin-induced diabetic Sprague-Dawley rats.

Utilization and Isolation of new active substances from Sericulture Related MaterialsI.Potentiation of Mulberry leaves for diseases attacking aged population

  • Lee, Won-Chu;Kim, Sun-Yeou
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 1997.06a
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    • pp.119-131
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    • 1997
  • As the average span of human life is continuously increasing, especially the old aged groups, are suffering from various chronic and critical diseases e.g. cardiovascular diseases, coronary heart disease, diabetes, atherosclerosis and alzheimer's etc. However, effective and safe treatment methods have not yet been investigated threathening old aged groups. This research was planned to isolate compounds with the therapeutic potential for the above mentioned chronic diseases from the mulberry leaves. Biological screenings were carried out for the following categories; anti-atherogenic, anti-diabetic and antihypertensive effects. The results were as follows; Mulberry leaves, 20% $\alpha$-treated Gaelyrangppong showed significant 81% of blood glucose lowering effects in alloxan-induced hyperglycemic mice. Particularly, butanol-soluble fractions of mulberry leaves showed the more significant hypoglycemic activity than other fractions in alloxan induced hyperhlycemic mice. Also in the group given 1g/kg doses of extract of mulberry leaves, total cholesterol level was decreased significantly by as much as 49% in hyperlipidemia-induced rats. In Mulberry leaves post-treated group, the atheroscelosis index, HDL-cholesterol/Total-cholesterol, was increased significantly by as much as 91%.