• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.671-678
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• 2007

Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Gamigukihwandong-hwan has been known to be effective for the treatment of diabetes. The present study was carried out to investigate the effect of Gamigukihwandong-hwan on renal function, peroxynitrite (ONOO$^-$) scavenging activity and polyol pathway in streptozotocin-induced diabetic rats. The crushed Gamigukihwandong-hwan was extracted 3 times, each time with 3 volumes of methyl alcohol at 60$^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 74.95 g. Gamigukihwandong-hwan extract was oral-administered 100 mg per 1 kg of body weight for 20 days to the diabetic rats induced by streptozotocin (60 mg/kg). The effects of Gamigukihwandong-hwan extract on the streptozotocin-induced diabetic rats were observed by measuring the serum level of glucose, insulin, lipid components, creatinine and BUN, and also the kidney levels of superoxide anion radical (${\cdot}O_2^-$), nitric oxide (NO) and ONOO$^-$, and also the enzyme activities involved in polyol pathway. The Effects of Gamigukihwandong-hwan on the streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin levels, creatinine and BUN levels, total cholesterol and triglyceride levels, and HDL-cholesterol levels were all shown to be good enough to cure and prevent the diabetes and its complications. Gamigukihwandong-hwan inhibited the generation of ${\cdot}O_2^-$, NO and ONOO$^-$ in the kidney of streptozotocin-induced diabetic rats. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the streptozotocin-induced diabetic rats, whereas the ones in the Gamigukihwandong-hwan administered group among the streptozotocin-induced diabetic rats were reversed toward the natural activities. Gamigukihwandong-hwan might inhibit the development of diabetic nephropathy by scavenging reactive oxygen and nitrogen species, thereby by reducing oxidative stresses and also by regulating the activities of polyol pathway enzymes, all of which could help to recover the function of kidney.

• The Korean Journal of Food And Nutrition
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• v.25 no.1
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• pp.99-104
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• 2012

The goal of this study was to examine the ameliorative effects of black ginseng(BG) in male obese diabetic C57BLKS/ J-db/db mice. Ten-week-old male db/db mice were administrated 300 mg/kg of F-BG daily for 6 weeks, The db/db mice where corresponded to the normal group and db/db mice which were the diabetic positive group were not provided BG treatment. The supressive effects of treatment were examined on serum lipids levels, which included total cholesterol, triglyceride, LDL-cholesterol and nonesterified fatty acid. Also, weight changes and the relative weight of liver and kidney, organ pathological investigation were measured. The effects of treatment were assessed by comparing the results of the db/db mice that received BG for 6 weeks with that of the diabetic positive group. Significant differences in several biological parameters such as HDL level(p<0.05), TG level(p<0.05) and NEFA level(p<0.05) were observed for the BG group. BG treatment increased the HDL level and decreased the NEFA level, which could ameliorate hyperlipidemia or blood circulation.

• Childhood Kidney Diseases
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• v.13 no.1
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• pp.1-13
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• 2009

Type 1 diabetes mellitus commonly occurs in childhood and adolescence, although the prevalence of type 2 diabetes mellitus in these age groups is now being increased in the western world and Korea. Diabetic nephropathy developing in 15-25% of subjects with type 1 diabetes mellitus and in similar or higher percentage of type 2 diabetes mellitus patients is the leading cause of end-stage renal disease worldwide. Although prepubertal diabetic duration may contribute less to the development of microvascular complications than pubertal and postpubertal duration, diabetic nephropathy in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to microalbuminuria or incipient DN. Type 1 diabetes is commonly associated with a period of hyperfiltration followed by the development of persistent microalbuminuria after as little as 7-10 years of type 1 diabetes. Microalbuminuria is associated with pathologic lesions that are so advanced as to overlap with those seen in patients with overt proteinuria and declining kidney function, therefore, microalbuminuria currently considered the best clinical indicator of overt diabetic nephropathy risk. This review covers the natural history and renal manifestations of diabetic nephropathy in children and adolescents.

• Journal of Life Science
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• v.20 no.5
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• pp.691-696
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• 2010

In this study, we investigated the antioxidative effects of So-Dang-Tang (SDT) on streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ (45 mg/kg body weight) into Sprague-Dawley rats. The SDT (200 mg/kg) and the reference drug, glibenclimide (1mg/kg), were orally administered once a day for 28 days in STZ-induced diabetic rats. The activity of antioxidant enzymes, including those of superoxide dismutase (SOD) and catalase, and the levels of glutathione (GSH) and production of malondialdehyde (MDA) were measured in the liver, kidney, and pancreas of diabetic rats. Treatment with SDT in STZ-induced diabetic rats significantly increased the activities of antioxidant enzymes and GSH levels in the liver, kidney, and pancreas when compared to those of the STZ-control group. SDT also significantly decreased lipid peroxidation product and MDA levels in STZ-induced diabetic rats. These results indicate that SDT has an antioxidative action in STZ-induced diabetic rats.

• Experimental and Molecular Medicine
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• v.51 no.2
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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.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.6
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• pp.704-712
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• 2013

This study was designed to examine the effects of bitter melon (BM) on the plasma blood glucose and cholesterol levels in diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats through an injection of streptozotocin (STZ) dissolved in a citrate buffer into the tail vein at a dose of 45 mg/kg of body weight. Sprague-Dawley rats were then fed for four weeks, with the experimental groups receiving a modified diet containing 5% or 10% powder derived from BM. The experimental groups were divided into 4 groups, consisting of the normal control group, STZ-control group and diabetic fed with BM 5% & 10% treated groups. The rats' body weight, blood glucose and cholesterol values were measured along with the hematocrit (Hct) values and aminotransferase activities. Body weight losses were observed in the diabetic groups, whereas the control rats gained weight. There were significant differences in kidney weight between the control group and the diabetic groups. The Hct levels of the diabetic BM-treated group were significantly higher than the STZ-control group. Aspartate aminotransferase activity was lower in the non-diabetic group compared to the diabetic experimental groups. Further, the blood glucose was significantly decreased in the 5% & 10% BM of the diabetic group. There were no significant difference in cholesterol levels among the diabetic groups. These results indicate that the supplementation of bitter melon may have a favorable influence on reducing the blood glucose level in STZ-induced diabetic rats.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.5
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• pp.1137-1143
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• 1999

This study investigated the effect of tea fungus/kombucha beverage(TF) protein concentrations and enzyme activities in serum of both normal and diabetic male rats. Sprague Dawley growing rats were randomly assigned to one control and five diabetic groups. In five diabetic groups, D control group was fed drinking water and the other groups were fed drinking water supplemented with 20 or 40% TF (20 or 40% TFD group, respectively) and 20 or 40% disinfected TF(20 or 40% TFSD group, respectively) for 7 weeks. Diabetes was experimentally induced in all five diabetic groups by streptozotocin injection after 3 week feeding. The diabetic groups were significantly decreased the body weight( 29.4~ 48.6g) compared with those in control group(72.4g). The total liver and kidney weights in all diabetic groups were similar to those in control group, but those relative to body weights in all diabetic groups were heavier than those in control group. The total spleen weight in all diabetic groups was significantly decreased compared with those in control group, but those relative to body weights in all diabetic groups were similar to those in control group. The blood glucose levels were heigher in all diabetic groups than those in control group. The alkaline phosphatase activity in serum was higher in all experimental groups than those in control group, but it was lower in 40% TFD, 20% and 40% TFSD groups than those in D control group. The GPT activity was significantly increased in D control, 20% and 40% TFD groups than in control group. The GOT activity was significantly increased in D control goup than in control group, but those in all TFD and TFSD groups were similar to control group. The total protein concentration in all diabetic groups was significantly decreased compared with that in control group, but the albumin concentration showed almost the same levels in all the experimental groups. The ratio of albumin/globulin, and hem atocrit value were significantly increased in all diabetic groups than in control group. These results show that tea fungus/kombucha beverage with which diabetic rats were fed has not recovered the decreased body weight, lowered serum total protein level, hypertrophy of liver and kidney, hyperglycemia to the normal state.

• Culinary science and hospitality research
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• v.13 no.3
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• pp.199-206
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• 2007

Hypoglycemic efficacy of natural functional mixture(FM) and level of the diabete related hormones in streptozotocin(STZ)-induced diabetic rats were investigated. Male Sprague-Dawley rats were divided into three groups (normal, diabetic fed diets with/without FM). Supplement of FM did not affect the body weight and feed intake of STZ-induced diabetic rats. The increase in the weight of liver of STZ-induced diabetic rats was weakened by supplement of FM, whereas the weight of kidney and heart was not affected. Blood glucose level was slightly, and glucose tolerance of post-feeding was significantly improved by functional mixture. The mixture significantly reduced the elevated HbA1C level of diabetic rats by 15%, and it increased the level of insulin and C-peptide in blood and decreased glucagon level. Therefore, we conclude that FM in this study has a potency of prevention and treatment of diabetes mellitus.

• Journal of Nutrition and Health
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• v.32 no.7
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• pp.767-774
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• 1999

This study was carrid out to examine a part of the mechanism for the etiology of diabetic complications. Thirty normal and forty streptozotocin(STZ)-induced diabetic rats were used as the animal models. Animals were sacrificed at the time points of 3 days, 1, 2, 4 and 6 weeks after STZ-injection and time course in body weight and organ weight, the levels of blood glucose, plasma lipid patterns, and atherogenic index were measured during 6 weeks. The STZ-diabetic animals showed 63% survival rate and fsting blood glucose levels of the diabetic animals measured in the range of 230-410mg/dL during the experimental period. The body weigh of diabetic animals decreased significantly throughout the experimental period and the relative weights of organs to body weight were significantly higher than the normal control ones. The enlargement of the kidney in the diabetic animals was especially remarkable. Plasma triglyceride concentration in diabetic rats substancially increased from the first week of onset of diabetes mellitus and maintained higher levels than the control ones throughout the whole experimental period. The plasma total cholesterol level and atherogenic index in the diabetic rats were significantly higher than the normal ones from the third day after STZ injection and showed a gradual increase with the duration of the disease. Throughout the experiment, the diabetic rats consistently showed a slightly lower HDL-cholesterol level compared to the normal animals. From the results of this study, it appears that the significant changes in blood lipid pattern in STZ-diabetic animals start from the first week after STZ injection.