• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.415-422
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• 2009

We previously demonstrated that zinc plus arachidonic acid (ZA) treatment lowered blood glucose levels in streptozotocin-induced diabetic rats, genetically diabetic obese (ob/ob) mice, and genetically diabetic, non-obese Goto-Kakizaki rats. However, plasma insulin levels did not increase with ZA treatment, suggesting that ZA lowers blood glucose levels not by stimulating pancreatic insulin secretion. However, it is unclear whether these agents lower blood glucose levels by decreasing hepatic glucose output (HGO) or by increasing glucose utilization in peripheral tissues, or both. In order to determine ZA target organ of insulin action, we divided 18 Sprague-Dawley rats weighing ${\sim}130g$ into 3 groups (6 rats per group) and treated them for four weeks with: (1) Control diet (regular rat chow), (2) High fructose (60.0%) diet only, and (3) the same fructose diet plus zinc (10 mg/L) and arachidonic acid (50 mg/L) containing drinking water. After 4 weeks, insulin action was assessed using the hyperinsulinemic euglycemic clamp technique. Food intake and body weights were comparable in all three groups of rats throughout the study period. Plasma glucose and insulin concentrations, glucose uptake, and HGO in the basal state were all the same in these three rat groups. During the clamp study, fructose-treated and fructose+ZA treated rat groups did not exhibit any detectable change on insulin-mediated glucose uptake compared to controls. High fructose feeding impaired insulin mediated suppression of HGO, compared to controls during clamp (4.39 vs. 2.35 mg/kg/min; p<0.05). However, ZA treatment in high fructose-fed rats showed a remarkable increase in hepatic insulin sensitivity compared to high fructose-fed rats, reflected by a complete recovery in suppression of HGO during the clamp (4.39 vs. 2.18 mg/kg/min; p<0.05). This data suggests that ZA increases insulin sensitivity in liver but not glucose utilization of peripheral tissues in high fructose-fed rats.

• Biomedical Science Letters
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• v.14 no.4
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• pp.233-238
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• 2008

Gestational diabetes mellitus (GDM) is a common complication during pregnancy and one of the main causes of adverse fetal-maternal outcomes. However, the pathogenesis of GDM has not been clearly stated. Adiponectin, an adipose tissue-derived plasma protein, is involved in regulation of insulin resistance and glucose hemostasis, and thus is a key modulator of insulin action and glucose metabolism. In this study, we investigated to compare serum adiponectin levels in pregnant women with diabetes, pregnant women who are without diabetes, and non-pregnant women, and to evaluate relationship between serum adiponectin. levels and metabolic parameters. Forty-one pregnant women with diabetes, fifty-nine pregnant women without diabetes and forty non-pregnancy women were recruited. Adiponectin levels were significantly lower in pregnant women with diabetes when compared to non-pregnant women and pregnant women without diabetes. Pregnant women without diabetes at second trimester had lower adiponectin levels compared to non-pregnant women. Adiponectin was negatively correlated with BMI, fasting insulin, HOMA-IR, total cholesterol, and triglyceride. In conclusion, this study confirmed that the decreased level of adiponectin precedes the onset of abnormal glucose level during pregnancy and also normal pregnant women had lower adiponectin levels compared to non-pregnant women. This knowledge may help to identify strategies for lowering the occurrence of GDM in women who are at high risk of developing the disorder.

• BMB Reports
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• v.45 no.6
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• pp.360-364
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• 2012

Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucose transporter 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane. Rab GTPases are involved in this vesicle trafficking, where Rab GTPases-activating proteins (RabGAP) enhance the GTP to GDP hydrolysis. TBC1D4 (AS160) and TBC1D1 are functional RabGAPs in the adipocytes and the skeletonal myocytes, respectively. These proteins contain two phosphotyrosine-binding domains (PTBs) at the amino-terminus of the catalytic RabGAP domain. The second PTB has been shown to interact with the cytoplasmic region of the insulin-regulated aminopeptidase (IRAP) of the GLUT4 vesicle. In this study, we quantitatively measured the ${\sim}{\mu}M$ affinity ($K_D$) between TBC1D4 PTB and IRAP using isothermal titration calorimetry, and further showed that IRAP residues 1-49 are the major region mediating this interaction. We also demonstrated that the IRAP residues 1-15 are necessary but not sufficient for the PTB interaction.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.71-77
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• 2012

Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal ${\beta}$-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

• Journal of the Korean Dietetic Association
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• v.7 no.3
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• pp.258-266
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• 2001

The purpose of this study was to investigate the effect of dietary zinc on the carbohydrate metabolism and the serum content of magnesium and chromium in rats fed normal diet. Animals were divided into three groups by different dietary zinc levels which were low(15ppm), normal(30ppm) or high(60ppm). Serum glucose and Insulin concentrations were assessed by the glucose method and the radio immuno assay respectively. Serum zinc. magnesium and chromium contents were measured by Indectively Coupled Plasma(ICP). Results of the study were as follows : 1. Feed intake in a zinc deficiency group was significantly higher than that in other group, but the weight gain in high zinc diet group was significantly lower than in other groups. 2. There were no significant differences in liver, kidney and spleen weight. 3. Serum glucose, insulin and zinc concentrations were not significantly different among different dietary zinc groups, However serum magnesium and chromium concentrations were significantly decreased as the level of dietary zinc was increased.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.2
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• pp.155-162
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• 1999

Euonymus alatus(Thunb.) Sieb has been used for cancer theraphy such as Liver cancer, esophagus cancer, stomach cancer, and uterine cancer in folk. Eupolyphaga simemsis(ES) extracted from Euonymus alatus(Thunb.) Sieb increases HDL-C/TC ratio and LCAT activity. TGF-${\beta}$ and Insulin has been Knoen as factors to induce the supression of proliferation of Hep3B, Human hepatoblastoma cell. Plasma HDL3-C involved in carbohydrate methabolism in the liver was maintained in low level by Euonymus alatus(Thunb.) Sieb. The low level of plasma HDL3-C suppresses the transition from normal liver to Fat liver. Finally, this resuly in suppression of cancer in liver. In this study, Euonymus alatus(Thunb.) Sieb showed higher cell toxicity in hepatoblastoma cell(Hep3B) compared to the uterine cancer cell(HeLa). This means Euonymus alatus(Thunb.) Sieb seems not to affect in the all kinds of cancer. In future, we will study whether Euonymus alatus(Thunb.) Sleb have an effect on the liver cancer induced by virus and hepatocellular carcinoma. Also, the mechanims of suppression of cell proliferation in HCC need to investigated.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• The Journal of the Korean dental association
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• v.47 no.2
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• pp.90-101
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• 2009

The aim of this study was to appraise the influence of conventional periodontal treatment on metabolic control in Korean type 2 diabetic patients. In addition, their periodontal change was compared with non-diabetic patients. Before and after treatment, it was performed to measure periodontal and metabolic indices in thirteen type 2 diabetic patients. Periodontal indices included plaque index, gingival index, bleeding on probing, probing pocket depth, gingival recession, and clinical attachment level. Metabolic indices included glycated hemoglobin(HbA1c), fasting plasma glucose, fasting plasma insulin, total cholesterol, triglyceride, and HDL-cholesterol. Plaque index, gingival index, bleeding on probing, probing pocket depth, and gingival recession showed significant improvements in the statistics. Diabetic patients showed no statistically significant differences in the changes of periodontal indices compared with non-diabetic patients. HbA1c values decreased in five of the thirteen subjects and fasting plasma glucose levels were reduced in four of the seven subjects after periodontal treatment. All five subjects whom HOMA values were calculated in showed the increases of insulin secretions. The results of this study ascertained the possibility of the better glycemic contol after conventional periodontal treatment in Korean type 2 diabetic patients and diabetes were well healed of their periodontal diseases after the treatment.

• CELLMED
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• v.2 no.3
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• pp.25.1-25.6
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• 2012

The aim of the present study was to evaluate the possible roles of hyperforin against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg). Biochemical parameters were measured following hyperforin treatment (10 mg/kg, i.p.) for 7 days. Hyperforin treatment significantly reversed the elevations in plasma glucose, triglycerides, total cholesterol and LDL-cholesterol. Hyperforin also reversed the declines in plasma HDL-cholesterol and liver glycogen, but did not reverse the change in plasma insulin levels when compared to the diabetic control rats. Hyperforin treatment also reversed the oxidative stress induced by streptozotocin. Moreover, the effect of the hyperforin on peripheral glucose utilization in normal rats was evaluated by an oral glucose tolerance test (OGTT). Hyperforin treatment significantly increased (p < 0.05) the glucose tolerance compared to the vehicle in OGTT. The antihyperglycemic, antihyperlipidemic and antioxidant activities of hyperforin (10 mg/kg, i.p.) were comparable qualitatively to glibenclamide (1 mg/kg, p.o.). In conclusion, we report for the first time through an in vivo study that hyperforin is potentially valuable for the treatment of diabetes and its associated hyperlipidemia and oxidative stress by enhancing the glucose utilization by peripheral tissues such as muscle and adipose tissues.

• Journal of Nutrition and Health
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• v.30 no.9
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• pp.1055-1060
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• 1997

The purpose of this study was to investigate the potential hypoglycemic effect of adlay diets when total fiber consumption was controlled in streptozotocin-induced diabetic rats. Forty eight rats were fed for 3 weeks with either controlled in streptozotocin -induced diabetic rats. Forty eight rats were fed for 3 weeks with either control diets or experimental diets : raw mille adlay (RMA) raw whole adlay(RWA) , steamed milled adlay(SMA) or roasted mille adlay(OMA). The composition of the AIN-76 diet was modified to ensure the same composition of protein, carbohydrate , rat, and fiber between the control diet and experimental diets. The concentrations of glucose , insulin, glycogen, and protein in plasma, liver, or skeletal muscle were compared . Compared to diabetic control rats, plasma postprandial glucose levels tended to be decreased in RMA, RWA, SMA and OMA rats until the 2nd week, but no difference was shown at the 3 rd week. There was no significant difference in insulin levels among those groups. After glucose loading, the plasma glucose level of SMA was lower than that of diabetic control rats throughout 2 hrs. Liver glycogen was lower than control values in RMA and RWA rats and not different in SMA and OMA rats. The muscle protein level of RMA, RWA, SMA, and OMA rats tended to be lower than in diabetic control rats. There was no significant difference in muscle glycogen among groups. These results suggest that the hypoglycemic effect of an adlay diet is not significant when the amount of total fiber consumption is controlled.