• 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.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.858-879
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• 2009

Objectives : The object of this study was to investigate the effects of Daeboeum-hwan (DBEH) aqueous extracts on Streptozotocin (STZ)-induced rat diabetes and related complications. Methods : SD rats were divided into 6 groups (n =8) : 50 mM citrate buffer and vehicle (distilled water 5 ml/kg) administered group (Intact control), STZ treatment (60 mg/kg, single intraperitoneally administered) and vehicle administered group (STZ control), STZ treatment and silymarin 100 mg/kg administered group (Reference), and STZ treatment and DBEH extracts 50, 100 and 200 mg/kg administered groups. DBEH extracts were orally administered once a day for 28 days from 3 weeks after STZ treatment. The results were compared with silymarin 100 mg/kg. Results : Decreases in the body weights, increase of kidney and liver weights, blood glucose, BUN, creatinine, AST, ALT, LDL, triglyceride and total cholesterol levels with decreases of HD L levels, increases of pancreatic MDA contents and decreases of GSH contents were detected in STZ control as compared with intact control. These diabetes and related complications were inhibited by treatment with 100 and 200 mg/kg of DBEH extracts. Conclusion : DBEH extracts showed favorable effects on STZ-induced diabetes and related complications mediated by their antioxidant effects as similar to silymarin. Because the lowest dosage (50 mg/kg) of DBEH treated group did not show any favorable effects as compared with STZ control, the effective dosages of DBEH is considered as about 100 mg/kg, while DBEH extracts at 200 mg/kg showed similar effects as compared with 100 mg/kg of silymarin. It, therefore, is expected that DBEH will show favorable effects on diabetes and various diabetic complications.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.683-690
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• 2011

The object of this study was to observe the effects of Hwanggeum-tang (HGT) aqueous extracts on Streptozotocin-induced rat's diabetes and related complications. Three different dosages of HGT extracts were orally administered oncea day for 28 days from 3 weeks after Streptozotocin treatment (60 mg/kg, single intraperitoneally administered). All the rats were checked at 3 weeks after Streptozotocin treatment as follows. Changes on the body weight, blood glucose level, kidney weight, serum BUN and creatinine level, liver weight, serum AST and ALT level, serum LDL, HDL, triglyceride and total cholesterol level were observed with changes on the pancreatic MDA content and GSH content. The results were compared with a potent antioxidant silymarin 100 mg/kg in which the effects on Streptozotocin-induced diabetes and related complications were already confirmed. As results of Streptozotocin-injected diabetes and related complications, dramatical decreases on the body weight, increase of the kidney and liver weight, increase of serum BUN, creatinine, AST, ALT, LDL, triglyceride, total cholesterol level and decreases of serum HDL level were detected in streptozotocin control as compared with intact control. In addition, marked increases of pancreatic MDA content and decreases of GSH content were also detected in streptozotocin control as compared with intact control. However, these diabetes and related complications, and inhibition of antioxidant effects induced by Streptozotocin were inhibited by 28 days continuous treatment of 50, 100 and 200 mg/kg of HGT extracts in the present study. HGT have favorable effects on the diabetes and various diabetic complications. Therefore, more detail mechanism studies should be conducedin future with the efficacy tests of individual herbal composition of HGT and the screening of the biological active compounds in herbs.

• Toxicological Research
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• v.12 no.2
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• pp.213-221
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• 1996

In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.2
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• pp.183-194
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• 1995

The purpose of this study was to investigate the effect of vitamin E on the synthesis of the metallothionein in the liver of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats($220{\pm}10mg$) were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were classified to STZ-0E(vitamine E free diet), STZ-40E(40mg vitamin E/kg of diet) and STZ-400E(400mg vitamin E/kg of diet) according to the level of vitamin E supplementation. Blood glucose levels of STZ-diabetic rats were three times higher than that of control. The contents of vitamin E in liver were lower signifciantly STZ-0E, STZ-40E groups by 50%, 36% compared with that of control. Lipid peroxide values(LPO) in liver were higher 5.6 and 2.5 times in STZ-0E and STZ-40E groups than that of control. Plasma cortisol levels were higher STZ-0E and STZ-40E groups compared with those of control, but cortisol levels were lower significantly in STZ-400E group compared with those of the STZ-0E and the STZ-40E groups. The plasma insulin levels were lower in all three STZ-diabetic group compared with that of control, but were not affected by the level of dietary vitamin E. The metallothionein (MT) contents in liver, kidney and small intestine were five times higher in STZ-0E, STZ-40E and STZ-400E compared with that of control, but STZ-400E group was lower in the MT contents in tissues compared with that of STZ-40E group. Zn-MT peak in STZ-diabetic rats liver increased than that of control by Sephadex G-75, and Zn-MT peak divided into MTI and MTII peaks by DEAE Sephadex A-25 column chromatography. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stress, leading to the acceleration of lipid peroxidation process, which can be more promoted low level of dietary vitamin E. And the result may that increase synthesis of MT induced in the liver of diabetic rats increased so it can be sure that the diabetes is one of the MT induce factor by free radical generation. And high vitamin E supplementation reduced total MT contents of liver, kidney and small intestine and the peak of purified Zn-MT. Through the results of these experiments, we can conclude that MT might be the free radical scavenger.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.3
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• pp.355-359
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• 2014

The objective of this study was to determine the hyperglycemic effects of mineral-rich salt in type 2 diabetic Goto-Kakizaki (GK) rats and normal Wistar rats. Animals were divided into five groups, including a normal group, fed three different experimental salts [purified salt (PS), mineral-rich salt (WS1 and WS2), and bamboo salt (BS)] in the form of 1% salt solution for 12 weeks. Liver, kidney, and spleen weights were significantly increased in GK rats of salt groups as compared to Wistar normal group without salt. However, there was no difference among the salt groups. For serum lipids, total cholesterol level in the BS group and triglyceride level in the WS group were significantly reduced compared to those of the PS group. The concentration of blood glucose in the GK-PS group increased continuously during the experimental period, whereas that in the GK-WS group was significantly reduced at 12 weeks. In GK rats, glucose levels among the salt groups in OGTT by glucose were not significantly different compared to normal rats. Insulin and glucagon levels in blood were not significantly different among the groups, and no such association was observed for insulin. Pancreatic lslets of Langerhans in the PS group showed irregular formation compared to those of the normal, WS, and BS groups.

• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.288-300
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• 2011

Objectives : The object of this study was to observe the effects of Hwangryungeehwang-tang (HRGHT), which has traditionally been used in Korean medicine for treating diabetes, by administering aqueous extracts to streptozotocin-induced diabetic rats. Methods : Three different dosages of HRGHT extracts were orally administered once a day for 28 days from 3 weeks after streptozotocin treatment (60 mg/kg, single intraperitoneally administered). 6 groups, of 8 rats per group were used in the present study, selected 3 weeks after streptozotocin treatment based on blood glucose levels and body weights. Changes to the body weights, blood glucose levels, serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels were observed, as well as changes on the pancreatic, hepatic and kidney malondialdehyde (MDA) contents for lipid peroxidation and glutathione contents for antioxidant effects. The results were compared with a potent antioxidant silymarin 100 mg/kg, of which the effects on streptozotocin-induced diabetes and related complications are already confirmed. Results : Significant decrease of blood glucose levels, serum LDL, total cholesterol, triglyceride levels, pancreatic, hepatic and renal MDA contents and significant increase of body weights, serum HDL levels, pancreatic, hepatic and renal GSH contents were detected in HRGHT extracts 100 and 200 mg/kg administered groups as compared to the streptozotocin control group. The lowest dosage of HRGHT treated group, 50 mg/kg, did not show any favorable effects as compared with the streptozotocin control. Conclusions : HRGHT has favorable effects on diabetes and related hyperlipidemia. Therefore, more detailed mechanism studies should be conduced in future with efficacy tests of individual herbal compositions of HRGHT and screening of the biological active compounds in the herbs.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.190-197
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• 2005

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications including nephropathy. However, the role of AGE in the activation of mesangial cells cultured under high glucose has not been elucidated. The effects of aminoguanidine, which prevents formation of AGE and protein cross-linking, on the synthesis of $TGF-{\beta}1$ and fibronectin by rat mesangial cells cultured under high glucose for 2 weeks were examined and compared with the effects of $N^G$-nitro-L-arginine methyl ester (NAME), a selective nitric oxide synthase inhibitor, because aminoguanidine also inhibits the inducible nitric oxide synthase. Culture of mesangial cells in 30 mM (high) glucose for 2 weeks induced 1.5-fold (ELISA) and 1.9-fold (Western blot analysis) increase in AGE in the culture media compared to 5.6 mM (control) glucose. Northern blot analysis revealed 1.5-fold increase in $TGF-{\beta}1$ and 1.7-fold increase in fibronectin mRNA expression in cells cultured under high glucose compared to control glucose. Increases in mRNA expression were followed by increased protein synthesis. Mink lung epithelial cell growth inhibition assay revealed 1.4-fold increase in $TGF-{\beta}1$ protein in high glucose media compared to control. Fibronectin protein also increased 2.1-fold that of control glucose by Western blot analysis. Administration of aminoguanidine suppressed AGE formation in a dose dependent manner and at the same time suppressed $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells cultured in both control and high glucose. In contrast, NAME did not affect high glucose-induced changes. These findings support a role for AGE in high glucose-induced upregulation of $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells.

• Journal of Ginseng Research
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• v.28 no.2
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• pp.111-119
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• 2004

The renoprotective effects of Korean Red Ginseng were examined in STZ-induced diabetic spontaneously hypertensive rats (SHR). After 3 day administration of streptozotocin (STZ), animals were divided into four groups : Group 1, hypertensive rats (H); Group 2, hypertensive rats with diabetes (HD); Group 3, hypertensive rats with diabetes administered with 100 mg/kg of ginseng total saponin(GTS); Group 4, hypertensive rats with diabetes administered with 600 mg/kg of ginseng non-saponin (GNS). After 2 weeks oral administraions of GTS and GNS, body weight, kidney weight, plasma glucose, urinary albumin excretion, serum creatinine, urea nitrogen and blood pressure were examined. After 3,7 and 21 day of STZ administration, expressions of TGF-${\beta}$1 and fibronectin in kidney were analyzed by immunoblotting and/or immunohistochemistry. GTS and GNS treatments slightly decreased blood pressure when compared to H and HD groups. Also, GTS and GNS treatments ameliorated kidney hypertrophy without affecting plasma glucose levels. Meanwhile, GNS treatment increased Cu/Zn-SOD activity in kidney and generally showed more efficient renoprotective effects than GTS. We suggest that the renoprotective effects of ginseng partially result from downregulations of TGF-${\beta}$1, fibronectin expressions and anti-oxidative activity of ginseng non-saponin.