• Childhood Kidney Diseases
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• v.9 no.2
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• pp.119-127
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• 2005

Purpose : Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, p-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. Methods : To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT-PCR. Results : We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. Conclusion : We suggest that high glucose with or without AGE suppresses the Production of P-cadherin at the transcriptional level and that these changes nay explain the functional changes of SD in diabetic conditions. (J Korean Soc Pediatr Nephrol 2005;9:119-127)

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.710-716
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• 2001

This study was conducted to examine the effects of dietary oligosaccharide on the blood glucose and serum lipid composition in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 150$\pm$10g were randomly assigned to one normal and four STZ-induced diabetic groups. Diabetic groups were classified to basal diet(DM group) 10% xylooligosaccharide diet(DM-XO group) 10% isomaltooligosaccharide(DM-IMO group) and 10% fructooligosaccharide (DM-FO). Diabetes was experimentally induced by intravenous injection of 50 mg/kg of body weight of STZ in citrate buffer (pH 4.3) after feeding of experimental diets for 4 weeks. The rats were fed with experimental diet for further 4 weeks in diabetic state. The oligosaccharide diets were not effected on the body weight food intakes and food efficiency ratio. The oligosaccharide diets were also not effected on the body weight food intakes and food efficiency ratio. The oligosaccharide diets were also not effected on the weights of liver kidney and small intestine but the weight of cecum was significantly increased on the groups of xylooligosaccharide and isomaltooligosaccharide diet. The levels of oral glucose tolerance test was more effectively improved by DM-XO group. The levels of blood glucose were markedly lower in oligosaccharide supplemented groups than that of DM group. The levels of blood glucose were markedly lower in oligosaccharide supplemented groups than that of DM group. Activities of two intestinal enzymes such as lactase and sucrase in DM-XO and DM-FO groups were lower than that of DM group while activity of maltase was lower only in DM-XO in DM-FO groups than that of DM-group respectively. The levels of serum triglyceride in DM-XO group were lower than that of DM-group respectively. The levels of serum triglyceride in DM-XO groups were lower than that of DM group however was no significant differences among the oligosaccharide groups. These results suggest that dietary oligosaccharide may act as functional food to be capable of improving carbohydrate and lipid metabolism in diabetic rats.

• The Journal of Internal Korean Medicine
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• v.27 no.4
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• pp.791-797
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• 2006

Objectives : The objective of the study was to observe the effects of different treatment lengths of Rhizoma Alismatis on diabetes mellitus. Methods : Rats were divided into three groups: normal(non-treated group), control (group administered saline for 4, 11, and 18 days), and RA (group administered 2.45mg/200g Rhizoma Alismatis for 4, 11, and 18 days). The experimental results were derived from the measurement of the levels of glucose, ALP, AST, ALT, creatinine and BUN in the serum from the rats on days 4, 11, and 18. Results : The glucose level in the serum significantly decreased on the 18th day. The ALP level in the serum did not show statistical significance. The GOT and GPT levels in the serum slightly decreased on the 4th, 11th, and 18th days, but did not show statistical significance. The creatinine level in the serum was unchanged for all of them. The BUN level in the serum did not show statistical significance. Conclusions : According to the above results, it is concluded that Rhizoma Alismatis has a therapeutic effect on diabetes mellitus with a longer period ofintake. As to influence upon the liver and kidney, there was no damage orside effects.

• Herbal Formula Science
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• v.14 no.2
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• pp.33-44
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• 2006

Objective : The objective of this study is to observe the effect of Yukmijiwhangtangkamibang(YukmD with Liriopis Tuber, Amomi Fructus, Citri Pericarpium, Zizyphi Spinosae Semen, Drynariae Rhizoma Ephedrae Herba, Ginseng Radix, Phellodendri Cortex, on the experimental diabetes. Methods : In order to induce diabetes experimentally, injected streptozoticin to the vein in the tail of rats and then treated oral administration of Yukmi water extracts. In the measurement of the variation levels of glucose, ALP, creatinine, and BUN concentration for each concentration levels for serum (382.5mg/l00g, 510.0mg/100g, 637.5mg/100g), concentration level of glucose significantly decreased in 510.0mg/l00g concentration level of Yukmi. With this 510.0mg/100g concentration level of Yukmijiwhangtanggamibang, the following conclusion was derived from the measurement of the serum levels of glucose, ALP, GOT, GPT, creatinine, and BUN concentration for the streptozotocin injection date of each 4th, 11th, and 18th day. Results : 1. In the measurement for each concentrations. the glucose concentration level in the serum significantly decreased on the 9th day in the Yukmi group. 2. In the measurement for each concentrations, the creatinine concentration level in the serum significantly decreased on the 9th day in the Yukmi group. 3. In the measurement for each dosage dates, the glucose concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/l00g administrated. 4. In the measurement for each dosage dates, the got concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/100g administrated. 5. In the measurement for each dosage dates, the creatinine concentration level in the serum significantly decreased on the 18th day in the Yukmi group to which 510.0mg/l00g administrated. Conclusion : Yukmi that is Yukmijiwhangtang with Liriopis Tuber, Amoni Fructus, Citri Pericarpium, Zizyphi Spinosae Semen, Drynariae Rhizoma, Ephedrae Herba, Ginseng Radix and Phellodendri Cortex, is known to have effects to lessen the damages on renal function and liver function without causing damages on liver and kidney.

• The Korea Journal of Herbology
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• v.32 no.4
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• pp.53-60
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• 2017

Objectives : Collagen decrease of Skin appears through various path ways. One of causes may be the Advanced glycation endproducts (AGEs) that combine formation of glucose and protein. The aim of this study was to explore the prevent wrinkle formation of Paeoniae radix (PR) and heated Paeoniae radix (HPR) via AGEs path way. Methods : AGEs formation inhibitory activities of PR and HPR measured using bovine serum albumin, glucose, and fructose. To evaluate the protective effects of PR and HPR in diabetic rats induced with streptozotocin (STZ) and methyl glyoxal (MGO), SD rat were distributed into four groups. Normal rats (Nor), AGEs-induced rats (Con), AGEs-induced rats treated with 100 mg/kg PR(PR), AGEs-induced rats treated with 100 mg/kg HPR (HPR). To induce AGEs, streptozotocin (50 mg/kg) was administered intraperitoneally and after 3 days administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of HPR inhibited AGEs in skin tissues compared with PR. The increased reactive oxygen species (ROS) levels in the serum were diminished by HPR treatment. The analyses of kidney and skin tissues proteins indicated that HPR treatment effectively reduced AGEs related protein levels as compared to that by PR treatment. Also, HPR decreased anti-oxidant related protein levels in skin tissues such as catalase, glutathione peroxidase. Moreover, it inhibited the reduction of COL1A2 by decreasing MMP-1. Conclusion : Based on these results, it was suggested that PR and HPR could have Improving effects on wrinkle formation. These evidences provide useful information for the development wrinkle formation treated agent.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.138-148
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• 2004

Purpose: Regardless of the underlying diseases, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes. We examined the molecular basis for this alteration of the podocyte phenotypes, including quantitative and distributional changes of ZO-1 protein as a candidate contributing to the pathogenic changes in the barrier to protein filtration. Methods: To investigate whether high glucose and advanced glycosylation endproduct(AGE) induce podocyte cytoskeletal changes, we cultured rat GEpC under 1) normal glucose(5 mM=control) or 2) high glucose(30 mM) or 3) AGE-added or 4) high glucose plus AGE-added conditions. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results: By confocal microscopy, we observed that ZO-1 moves from peripheral cytoplasm to inner actin filaments complexes in both AGE-added and high glucose condition. In Western blotting, high glucose or AGE-added condition decreased the ZO-1 protein expression by 11.1%(P>0.05) and 2.3%(P>0.05), respectively compared to the normal glucose condition. High glucose plus AGE-added condition further decreased ZO-1 protein expression to statistically significant level(12%, P<0.05). No significant change was seen in the osmotic control. In RT-PCR, high glucose plus AGE-added condition significantly decreased the expression of ZO-1 mRNA by 12% compared to normal glucose condition. Conclusion: We suggest that both high glucose and AGE-added condition induce the cytoplasmic translocation and suppresses the production of ZO-1 at transcriptional level and these changes may explain the functional changes of podocytes in diabetic conditions.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.8-17
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• 2006

Purpose : We describe the changes of rat glomerular epithelial cells when exposed to high levels of glucose and advanced glycosylation endproducts(AGE) in the in vitro diabetic condition. We expect morphological alteration of glomerular epithelial cells and permeability changes experimentally and we may correlate the results with a mechanism of proteinuria in DM. Methods : We made 0.2 M glucose-6-phsphate solution mixed with PBS(pH 7.4) containing 50 mg/mL BSA and pretense inhibitor for preparation of AGE. As control, we used BSA. We manufactured and symbolized five culture dishes as follows; B5 - normal glucose(5 mM) + BSA, B30 - high glucose(30 mM) + BSA, A5 - normal glucose(5 mM) + AGE, A30 - high glucose(30 mM) + AGE, A/B 25 - normal glucose(5 mM) + 25 mM of mannitol(osmotic control). After the incubation period of both two days and seven days, we measured the amount of heparan sulfate proteoglycan(HSPG) in each dish by ELISA and compared them with the B5 dish at 2nd and 7th incubation days. We observed the morphological changes of epithelial cells in each culture dish using scanning electron microscopy(SEM). We tried the permeability assay of glomerular epithelial cells using cellulose semi-permeable membrane measuring the amount of filtered BSA through the apical chamber for 2 hours by sandwich ELISA. Results : On the 2nd incubation day, there was no significant difference in the amount of HSPG between the 5 culture dishes. But on the 7th incubation day, the amount of HSPG increased by 10% compared with the B5 dish on the 2nd day except the A30 dish(P<0.05). Compared with the B5 dish on the 7th day the amount of HSPG in A30 and B30 dish decreased to 77.8% and 95.3% of baseline, respectively(P>0.05). In the osmotic control group (A/B 25) no significant correlation was observed. On the SEM, we could see the separated intercellular junction and fused microvilli of glomerular epithelial cells in the culture dishes where AGE was added. The permeability of BSA increased by 19% only in the A30 dish on the 7th day compared with B5 dish on the 7th day in the permeability assay(P<0.05). Conclusion: We observed not only the role of a high level of glucose and AGE in decreasing the production of HSPG of glomerular epithelial cells in vitro, but also their additive effect. However, the role of AGE is greater than that of glucose. These results seems to correlate with the defects in charge selective barrier. Morphological changes of the disruption of intercellular junction and fused microvilli of glomerular epithelial cells seem to correlate with the defects in size-selective barrier. Therefore, we can explain the increased permeability of glomerular epithelial units in the in vitro diabetic condition.