• The Korea Journal of Herbology
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• v.29 no.5
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• pp.75-81
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• 2014

Objectives : This study was performed to investigate the effect of root extract of Pueraria thunbergiana Bentham (Puerariae Radix, PR) in diabetic mice as similar as emaciation-thirst disease in Oriental medicine. Methods : C57BL/6 mice were fed high fat (HF) and high sucrose (HS) for 8 weeks, and then administrated with 90 mg/kg body weight (bw) of streptozotocin (STZ) for induction of diabetes which is similar to the middle emaciation stage. After 5 days, blood glucose levels were measured, and selected the mice with ranges above $250mg/d{\ell}$. PR water extract was administrated orally once a day for 4 weeks with high fat and high sucrose. The levels of glucose, insulin, total cholesterol, triglyceride, ${\gamma}glutamyl$ transpeptidase (${\gamma}GTP$), glutamic oxaloacetic transaminase (GOT) and glutamate pyruvate transaminase (GPT) were analysed in the serum. Also, observed their histological changes by hematoxylin and eosin (H&E) of different organs, lung, heart, pancreas, stomach, liver, and kidney. Results : PR extract significantly decreased the levels of serum glucose and insulin in diabetic mice. PR extract significantly increased the levels of triglyceride, total cholesterol, GOT and GPT in diabetic mice. In H&E stain, PR extract inhibited the histopathological changes of lung (as a channel of the upper emaciation stage in the channel-tropism theory), pancreas (as a channel of the middle emaciation stage) and kidney (as a channel of the lower emaciation stage) in diabetic damage. Conclusions : PR extract has an anti-diabetic effect in HF/HS and low-dose STZ-induced diabetic mice. This result suggests that PR follows the channel-tropism theory in the emaciation-thirst disease through the protection of lung, pancreas and kidney.

• Journal of Life Science
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• v.23 no.6
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• pp.825-831
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• 2013

The aim of this study was to investigate the effects of induced diabetes by streptozotocin (STZ) administration on gene expression of proinflammatory cytokines in adipose tissue of C57/BL6 mice fed either a normal diet (ND) or a high-fat diet (HFD). Four diabetic mice groups (16- or 26-week-old mice fed either ND or HFD) and four control groups of age and diet matched non-diabetic mice were used. By real-time PCR, gene expression levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and monocyte chemoattractant protein-1 (MCP-1) were examined in adipose tissue. The results demonstrated that gene expression of TNF-${\alpha}$ was significantly or marginally increased in STZ induced diabetic mice groups compared with non-diabetic groups. On the other hand, MCP-1 gene expression tended to be decreased in diabetic mice compared with non-diabetic controls. Especially, MCP-1 expression level in 16w diabetic mice on HFD was about 26% of that in age and diet matched non-diabetic controls (p<0.001). In addition, MCP-1 gene expression in adipose tissue was correlated with plasma insulin levels (p=0.0002). These results suggest that gene expression of proinflammatory cytokines in adipose tissue is differentially regulated in mouse models of diabetes. The basic data in this study will be useful for elucidating basic mechanisms of inflammatory state and increased expression of proinflammatory cytokines in adipose tissue in obesity, insulin resistance, and diabetes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1497-1501
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• 2006

The therapeutic anti-diabetic effect of Nelumbo Folium and a poly herbal formula (NOC) was evaluated in the streptozotocin (STZ 60 mg/kg, I.p.) induced diabetic rats. For this study, test articles were orally administrated once a day from 7 d after STZ-injection for 3 weeks. The fasting blood glucose, body weight, pancreas weight changes, oral glucose tolerance test, hemoglobin Alc (Hb A1c) level changes and the histopathological changes were observed. WNL-treated rat had lower fasting blood glucose levels compared to control group and NOC-treated rat had significantly lower fasting blood glucose levels, compared to control group (p < 0.05). After 21 days of extract treatment, body weight in control was reduced (p < 0.001). WNL and NOC groups were also reduced compared to control group but insignificantly. Pancreas weight of control group was reduced (p < 0.001), but the weight of NOC group were increased (P< 0.05). During the 2 h oral glucose tolerance test (OGTT), WNL group were improved compared to control group (P < 0.05). NOC group were improved compared to control group but insignificantly. WNL and NOC groups had lower Hb Alc level compared to control group. In addition, atrophy of islet and decrease of insulin-producing cells were detected in STZ induced diabetes rats. However, these diabetic changes were decreased in WNL and NOC groups. These results suggest that N. Folium and NOC have favorable effects to inhibit the changes on the fasting blood glucose levels, pancreas weight, glucose tolerance, hemoglobin Alc and the histopathological changes of pancreas in STZ-induced diabetes.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.489-496
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• 2000

This study was conducted to investigate the effects of streptozotocin-induced (STZ) diabetes on insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBPs), and IGF-I carrier proteins in serum, liver, and kidney. The levels of total and free IGF-I were measured by radioimmunoassay (RIA). The patterns of IGFBPs were determined by western ligand blotting (WLB) analysis. The profiles of IGF-I carrier proteins in serum were determined by column chromatography. The levels of total and free IGF-I in serum were lower in STZ-induced diabetic rat than normal rat (p<0.01). Similarly, the levels of total IGF-I in liver was lowered in STZ-induced diabetic rats. On the other hand, the levels of total IGF-I in kidney were increased in STZ-induced diabetic rats compared with normal rats (p<0.01). In serum and liver from STZ-induced diabetic rats, the amount of IGFBP-3 was decreased and the amount of IGFBP-2 was increased compared with normal rats. There was a not difference in amount of IGFBP-4 in serum between STZ-induced diabetic rats and normal rats. The serums of normal rats have higher 150kDa carrier proteins than in STZ-induced diabetic rats, whereas, most of 50kDa carrier proteins were found in STZ-induced diabetic rats. These results demonstrate that in STZ-induced diabetic rats, IGF-I/IGFBPs system that included functional bioactivity was changed in serum as well as tissues, and these changes may play an important role in pathogenesis of diabetes.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.87-93
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• 2005

This study investigated the response of GLUT -4 and GRP-78 expression in soleus muscle of streptozotocin-induced diabetic rats by imposing different exercise intensities. F344 rats were randomly divided into 4 groups (n=15 in each group): Control (Control), diabetes-operation (DO), diabetes with low intensity exercise (DLE) and diabetes with high intensity exercise (DHE). The rats in DLE and DHE groups were exercised for 8 weeks by treadmill running. Blood glucose levels in DO were significantly higher compared to that in NORMAL whereas DLE showed the most lowest level in blood glucose among diabetic groups. Diabetic groups exhibited significantly lower level in insulin change and DLE showed significantly higher insulin level among diabetic groups. GRP-78 in DO was significantly $(167.05\%)$ higher than that in Control. GRP-78 in DLE was $139.41\%$ which is significantly higher compared to Control but when compared to DO and DHE, it was significant low. GRP-78 in DHE was $194.64\%$ which doubled the protein level in Control and showed the most highest level in all groups. GLUT-4 in DO was significantly $(33.58\%)$ higher compared to Control. GLUT-4 in DLE showed $124.58\%$ which was significant high compared to Control, DO and DHE. GLUT-4 in DHE showed $26.91\%$ compared to Control and was the most lowest level among all groups. It seems clear that chiefly low intensity exercise benefits diabetic patients in controlling blood glucose. It was concluded that low intensity exercise induces translocation of GLUT-4 which results in increased blood inflow, thus GRP-78 expression is decreased.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.8
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• pp.1337-1343
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• 2003

Diabetes mellitus has been known to be a state of increased oxidative stress. Free radical formation and lipid peroxidation are accelerated in this metabolic disorder. Buchu (Allium tuberosum Rottler) contains lots of antioxidative nutrients such as chlorophyll, vitamin C, $\beta$-carotene, phenolic compounds and sulfur compounds. To investigate the protective effects of buchu, 10% lyophilized buchu diet was fed to streptozotocin (STZ)-induced diabetic rats for 14 weeks and lipid peroxidation, protein oxidation, contents of reactive oxygen species, activities of antioxidative enzymes and contents of accumulated lipofuscin were measured as indicators of oxidative stress. Hepatic MDA and carbonyl contents tended to decrease in 10% buchu diet group compared with control group. Dietary buchu significantly suppressed lipid and protein oxidation in the skin of rats (p<0.05). Contents of hepatic hydroxyl radicals, which exert the highest toxicity among the reactive oxygen species, were significantly decreased in rats fed 10% buchu diet (P<0.05). Activities of antioxidative enzyme, such as superoxide dismutase, catalase, and glutathione peroxidase, tended to increase in liver and skin of rats fed 10% buchu diet, while hepatic catalase activity was significantly increased in buchu group compared with control group. Buchu supplementation significantly inhibited the accumulation of lipofuscin, an end-product of lipid peroxidation reactions induced by reactive oxygen radicals, in eye tissues compared with control diet (p<0.001). In conclusion, buchu supplementation diminished the oxidative stress, so dietary buchu could help to attenuate diabetes complications.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.13-25
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• 2008

The purpose of this study was to investigate extract from mixed culture with Trichloloma matsutake mycelium in oriental medicine and cereal medium(OCM) to develop new material for pharmaceutical products and medicinal food for diabetes mellitus. To evaluate of hypoglycemic activity of OCM extracts, we examined the inhibitory activity of ${\alpha}$-glucosidasein OCM, blood glucose level and liver function of streptozotocin(STZ) induced diabetic rat. Experimental group was divided into 6 groups: first, it was divided into normal control group(hereafter NC group) and diabetes-induced group, and diabetes-induced group was subdivided into diabetic control group(DC group), treated by hot water extracts group(HE), ultra sonic waves, micro waves, and micro bubble extracts g roup(UE), crude polysaccharide of HE group (HEE) and crude polysaccharide of UE group(UEE) at a dose of 300mg/kg/body weight, respectively. In diabetic-induced groups, after streptozotocin was melted in 0.01M citrate buffer at 50mg/kg/body weight, when the non-fasting blood glucose levelwas 300 mg/dl or more in blood collected from the tail vein, it was regarded as diabetic induction and then such diabetic-induced experimental animals were used in this experiment. At the end of the experiment, blood glucose level increased by 4.19% in DC group but significantly decreased by 32.34%, 19.19%, 17.81% and 17.64%, respectively in UEEE, UE, HE, and HEE groups. In the cases of AST, ALT, and ALP, the experiment group treated with extracts showed significantly lowerblood glucose level than DC group. The levels of BUN and uric acid were found to be lower in the UMPM extract group(UE) than HW extract group(HE), which implies that herb medicine medium extracts in which Tricholoma matsutake mycelia were cultured are effective in reducing impaired liver function as well as high blood glucose level caused by diabetes. In addition, the administration of low temperature UMPM extracts was found to produce better results than that of high temperature hot water extracts. In this regard, it is expected that extracts from herb medicine obtained by cultivating Tricholoma matsutake mycelia will be widely used as new ingredients for foods and medicines for prevention and treatment of diabetes.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.253-261
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• 1993

Possible changes in the role of insulin-sensitive cyclic nucleotide phosphodiesterase(PDE) in mediating the antilipolytic action of insulin were investigated in adipocytes from streptozotocin-induced diabetic rats. Isolated adipocytes prepared from epididymal adipose tissue were incubated, with or without insulin, at $37^{\circ}C$ for 15 min following pretreatment with various drugs or toxins, and three (plasma membranes, microsomal membranes, and cytosol) fractions prepared by differential centrifugation were then assayed for cAMP phosphodiesterase activity. The PDE activities only in the crude microsomal (P2) fractions were activated by insulin both in diabetic and control rats. The basal PDE activities in P2 fractions of adipocytes from diabetic rats were higher than those from control rats, although the maximal effects observed at 2 nM of insulin, $100\;{\mu}M$ of isoproterenol or the combination of both were not significantly different from each other. The insulin-stimulated PDE activities in P2 fractions of adipocytes from diabetic rats were not changed by PIA, a $A_{1}$ adenosine receptor agonist, whereas they were decreased to the basal PDE activities in those from control rats. In addition, the adipocytes from diabetic rats showed an increased sensitivity to pertussis toxin compared to those from controls. There were no differences between diabetic and control rats in the sensitivity of adipocytes to cholera toxin. These data indicate that the impaired signalling through inhibitory receptors such as adenosine receptors in adipocytes from streptozotocin-induced diabetes relates to the loss or the decreased function of $G_i$ proteins, and leads to the increased activity of the insulin-dependent PDE at the basal states.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.231-236
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• 1996

In our previous study (Kim et al, 1991), GLUT 4 protein content correlated negatively with plasma glucose levels in skeletal muscles of STZ-induced diabetic rats. Thus, in this study, to confirm whether expression of GLUT 4 correlate negatively with degree of hyperglycemia, we measured levels of GLUT 4 mRNA in red and white gastrocnemius muscles in STZ-induced mild and severe diabetic rats. Rats were randomly assigned to control, mild, and severe diabetic groups, and the diabetes was induced by intraperitoneal administration of STZ. The experiment was carried out 10 days after STZ administration. Gastrocnemius red and white muscles were used fur the measurement of GLUT 4 expression. Plasma glucose levels of mild and severe diabetic rats were increased compared to control rats (control, mild, and severe diabetes; $6.4{\pm}0.32,\;9.4{\pm}0.68,\;and\;22.0{\pm}0.58$ mmol/L, respectively). Plasma insulin levels of mild and severe diabetic rats were decreased compared to control rats (control, mild, and severe diabetes; $198{\pm}37,\;l14{\pm}14,\;and\;90{\pm}15$ pmol/L, respectively). GLUT 4 mRNA levels of gastrocnemius red muscles in mild and severe diabetic rats were decreased compared to control rats ($64{\pm}1.2%\;and\;71{\pm}2.0%$ of control, respectively), but GLUT 4 mRNA levels in gastrocnemius white muscles were unaltered in diabetic rats. In summary, GLUT 4 mRNA levels were decreased in STZ-induced diabetic rats but did not correlated negatively with degree of hyperglycemia, and this result suggest that the regulatory mechanisms of decreased GLUT 4 mRNA levels are hypoinsulinemia and/or other metabolic factor but not hyperglycemia. And regulation of GLUT 4 expression in STZ-induced diabetes between red and white enriched skeletal muscles may be related to a fiber specific gene regulatory mechanism.

• Nutritional Sciences
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• v.7 no.3
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• pp.127-132
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• 2004

The current study examined the effects of mulberry fruit on the antioxidative defense systems and oxidative stress in the erythrocytes of diabetes-induced rats. Sprague-Dawley male rats were randomly assigned to one normal and three streptozotocin (STZ)-induced diabetic groups. 1be diabetic groups were fed a mulberry fruit-free diet (DM-group), 0.3% mulberry fruit diet (DM-F group) or 0.6% mulberry fruit diet (DM-2F group). Diabetes was induced with STZ after three weeks of the experimental diets. 1be rats were sacrificed 9 days later for examination of the antioxidative defense systems and oxidative stress in the erythrocytes. Means of cy-3-Ο-glucopyranoside, cy-3-Ο-rutinoside, rutin, isoquercitrin, quercetin, morin and dehydroquercetin contents were 230.45, 131.5, 142.5, 10.3, 5.8, 1.6 and 3.83mg per l00g dry weight, respectively, in the mulberry fruit. Mulberry fruit strengthened the antioxidative defense systems through increased activity of the antioxidant enzymes, such as glutathione peroxidase (GSH-px) and catalase (CAT), in the erythrocytes of the diabetes-induced rats. Accrdingly, mulberry fruit was found to reduce the accumulation of thiobarbituric acid reactive substance (WARS). Therefore, mulberry fruit was found to be excellent for strengthening the antioxidative defense system and reducing damaging oxidative substances in the erythrocytes of the diabetes-induced rats.