• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.497-505
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• 2004

The proliferation of mesangial cells has been associated with the development of diabetic nephropathy. The cell proliferation has been regulated by diverse growth factors. Among them, insulin like growth factors(IGFs) are also involved in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion and the relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in the mesangial cells. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. High glucose(25 mM) increased IGF-I and IGF-II secretion. High glucose-induced increase of IGF-I and IGF-II secretion were blocked by taurine($2{\times}10^{-3}$ M), N-acetyl cystein(NAC, $10^{-5}M$), or GSH($10^{-5}M$) (antioxidants), suggesting the role of oxidative stress. High glucose-induced secretion of IGF-I and IGF-II were blocked by H-7, staurosporine, and bisindolylmaleimide I(protein kinase C inhibitors). On the other hand, high glucose also increased lipid peroxide (LPO) formation in a dose dependent manner. In addition, high glucoseinduced stimulation of LPO formation was blocked by PKC inhibitors. These results suggest that PKC is responsible for the increase of oxidative stress in the action of high glucose-induced secretion of IGF-I and IGF-II in mesangial cells. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via PKCoxidative stress signal pathways in mesangial cells.

• Journal of the Korea Convergence Society
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• v.10 no.8
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• pp.299-308
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• 2019

The purpose of this study was to confirm if self-management and self-efficacy of diabetic nephropathy hemodialysis patients were influencing factors on the hemodialysis-related symptoms. A cross-sectional study was performed on 254 patients based at 3 University hospital hemodialysis centers and 7 hemodialysis clinics from September 2017 to November 2017. The data was analyzed using t-test, ANOVA, Scheffe test, Pearson correlation, and multiple regression analysis. The results showed that patients with stable economic condition and no complications from diabetes, the higher patient self-management and self-efficacy led to lower hemodialysis related symptoms. Therefore, the government should provide financial support, a management process needs to be set up to prevent complications from diabetes, and disease-specific patient self-management program should be implemented to increase patient's self-efficacy.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.256-262
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• 2009

Smallanthus sonchifolius (Yacon, Asteraceae) was originally cultivated in South America and used in food and traditional medicine by Andean inhabitants. Yacon is potentially beneficial for the management of diabetes and is composed of fructooligosaccharides, proteins, minerals and phenolic compounds. The aim of this study was to investigate the hypoglycemic effect of Yacon tuber extract (YTE) and its constituent, chlorogenic acid (CGA), in streptozotocin (STZ)-induced diabetic rats. In this study, a HPLC method was developed for simultaneous determination of major active phenolic components, CGA and caffeic acid in YTE. We investigated the hypoglycemic effect of YTE and CGA in STZ-induced diabetic rats and studied glucose tolerance test (GTT). The effect of orally administered multiple doses of YTE and CGA on plasma biochemical parameters was examined using diabetic rats. We also measured free radical scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Oral administration of YTE (200 mg/kg) and CGA (10 mg/kg) for 6 weeks produced a significant hypoglycemic effect in STZ-induced diabetic rats. YTE and CGA-treated groups exhibited significantly decreased plasma glucose surge during the GTT. Total cholesterol (TC) and triglyceride (TG) concentrations were significantly decreased by 33% and 49%, respectively, in YTE-treated rats. TC and TG concentrations were also significantly decreased by 26 % and 41%, respectively, in CGA-treated rats. In the DPPH assay, free radical scavenging activity of CGA was similar to that of vitamin E, a positive control. This study suggests that YTE and its constituent, CGA, may be a useful option for management of hyperglycemia and diabetic nephropathy.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.233-238
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• 2014

Background: The actin cytoskeleton in podocytes is essential for the maintenance of its normal structure and function. Its disruption is a feature of podocyte foot-process effacement and is associated with proteinuria. ${\alpha}$-Actinin-4 in podocytes serves as a linker protein binding the actin filaments of the cytoskeleton. Methods: To investigate the effect of ginseng total saponin (GTS) on the pathological changes of podocyte ${\alpha}$-actinin-4 induced by diabetic conditions, we cultured mouse podocytes under normal glucose (5mM) or high glucose (HG, 30mM) conditions, with or without the addition of advanced glycosylation end products (AGE), and treated with GTS. Results: In confocal imaging, ${\alpha}$-actinin-4 colocalized with the ends of F-actin fibers in cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated ${\alpha}$-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated ${\alpha}$-actinin protein in a time- and dose-dependent manner, and suppressed the receptor for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and both together, decreased cellular ${\alpha}$-actinin-4 protein levels at 24 h and 48 h. Such quantitative and qualitative changes of ${\alpha}$-actinin-4 protein induced by diabetic conditions were mitigated by GTS. Conclusion: These findings imply that both HG and AGE have an influence on the distribution and amount of ${\alpha}$-actinin-4 in podocytes that can be recovered by GTS.

• Biomedical Science Letters
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• v.17 no.4
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• pp.337-345
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• 2011

It is well recognized that conventional coronary artery bypass grafting (ONCAB) often leads to major organ dysfunction including renal injury. Diabetes mellitus is a major cause of nephropathy and poor clinical outcomes. The aim of this retrospective study was to evaluate the occurrence of adverse outcomes including renal impairment between diabetic (n=75, DM group) and non-diabetic patients (n=72, Non-DM group) underwent off-pump coronary artery bypass grafting surgery (OPCAB). Fasting glucose, hemoglobin A1c, fructosamine, fibrinogen and serum osmolality levels in the DM group were higher than those of the Non-DM group at pre-operative (Pre-OP) period ($P$ <0.05). History of hypertension and renal impairment in the DM group was higher than that of the Non-DM group ($P$ <0.05). Potassium ($K^+$), blood urea nitrogen and creatinine levels were higher, whereas sodium ($Na^+$) and glomerular filtration rate (GFR) levels were lower in the DM group than the Non-DM group at peri-operative period ($P$ <0.05). Fasting glucose levels at Pre-OP period had positive correlations with blood urea nitrogen and creatinine levels at peri-operative period, but negative correlations with GFR levels at peri-operative period in the DM group ($P$ <0.05). Incidences of renal impairment, diuretic therapy or continuous renal replacement therapy and fever in the DM group were higher than those of the Non-DM group at post-operative period ($P$ <0.05). These results suggest that blood glucose level should be tightly controlled at peri-operative period to avoid renal dysfunction in diabetic patients.

• Toxicological Research
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• v.27 no.1
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• pp.37-41
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• 2011

This study investigated the antioxidative action of Corni Fructus aqueous extract on kidneys of diabetic mice. The electron donating abilities of Corni Fructus aqueous extract and its antioxidant activities (XO, SOD, CAT, GST, eNOS) in kidneys of C57BL/6 or db/db mice were evaluated. For in vivo study, seven week-old male mice were divided into normal control group (NC, C57BL/6 mice), diabetic control group (DC, db/db mice) and Corni Fructus (500 mg/kg/day for 8 weeks) treated diabetic group (DCF, db/db mice). The electron donating abilities of Corni Fructus aqueous extract exhibited 7%, 24.4%, and 42.7% at concentrations of 100, 500, and $1000\;{\mu}g/ml$, respectively. The activity of XO in the DCF group was significantly lower than the DC group by 35% (p < 0.05). The SOD activity was significantly higher in the DCF group than the DC group by 26% (p < 0.05). The activities of CAT and GST were lowered in the DCF group than the DC group by 26% (p < 0.05) and 7.6%, respectively. The mRNA expression of eNOS in kidneys was lower in the DCF group than the DC group by 24%. These results indicate that Corni Fructus reduced oxidation stress as evidenced by the restoration of the enzymatic antioxidative defense system in renal tissues of db/db mice. It is suggested that these antioxidative actions of Corni Fructus on renal tissues in db/db mice could contribute to its renoprotective effects on diabetic nephropathy.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.85-91
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• 2019

Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.

• Reproductive and Developmental Biology
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• v.34 no.4
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• pp.299-304
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• 2010

To identify the treatment effect of lactic acid bacteria for diabetes, the treatment effects of a single administration of acarbose (a diabetes treatment drug) or lactic acid bacteria, and the mixture of acarbose and lactic acid bacteria on diabetes in a type 1 diabetes animal model, were studied. In this study, streptozotocin was inoculated into a Sprague-Dawley rat to induce diabetes, and sham control (Sham), diabetic control (STZ), STZ and composition with live cell, STZ and composition with heat killed cell, STZ and composition with drugs (acarbose) were orally administered. Then the treatment effect on diabetes was observed by measuring the body weight, blood glucose, and serum lipid. For the histopathological examination of the pancreas, the Langerhans islet of the pancreas was observed using hematoxylin and eosin staining, and the renal cortex, outer medullar, and inner medullar were also observed. The induced diabetes decreased the body weight, and the fasting blood glucose level decreased in the lactic-acid-bacteria-administered group and the mixture-administered group. In addition, the probiotic resulted in the greatest decrease in the serum cholesterol level, which is closely related to diabetes. Also, the hematoxylin and eosin staining of the Langerhans islet showed that the reduction in the size of the Langerhans islet slowed in the lactic-acid-bacteria-administered group. The histopathological examination confirmed that the symptoms of diabetic nephropathy decreased in the group to which viable bacteria and acarbose were administered, unlike in the group to which dead bacteria was administered. The mixture of lactic acid bacteria and acarbose and the single administration of lactic acid bacteria or acarbose had treatment effects on the size of the Langerhans islet and of the kidney histopathology. Thus, it is believed that lactic acid bacteria have treatment effects on diabetes and can be used as supplements for the treatment of diabetes.

• Journal of Nutrition and Health
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• v.53 no.1
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• pp.1-12
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• 2020

Purpose: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway. Methods: Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1-20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis. Results: High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1-20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin. Conclusion: These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.

• International Journal of Industrial Entomology and Biomaterials
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• v.5 no.2
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• pp.201-204
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• 2002

This study was undertaken to find effects of ethanol extracts from Bombyx mori on the hyperglycemia induced by streptozotocin in rats. Blood glucose level of rats increased depending on experimental days after streptozotocin treatment. But there was no difference in blood glucose level between the rats injected with ethanol extracts of B. mori and normal rats. There was no significant difference in the kidney fibrosis between the rats injected with ethanol extrscts of B. mori and normal rats at all ages examined. The transforming growth factor-$\beta$l ($TGF-{\beta}1$) protein was detected in the glomerulay endothelial cells and tubular epithelial cells of streptozotocin rats at 14 days of age. In the rats injected with ethanol extracts of B. mori to the kidneys, the $TGF-{\beta}1$ protein was detected very faintly. The $TGF-{\beta}1$ mRNA of streptozotocin rats increased at 14 days of age, and this was higher than the rats injected with ethanol extrscts of B. mori. Taken these together, the results suggest that the ethanol extracts of B. mori ameliorate hyperglycemia of the rats induced by streptozotocin.