• Korean Journal of Food Science and Technology
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• v.36 no.3
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• pp.472-477
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• 2004

Hypoglycemie effect of Moutan Radicis Cortex (MRC) extract contained in Yukmijihuang-hwan was determined by investigating insulin-sensitizing and ${\alpha}-glucoamylase-suppressing$ actions. MRC was extracted with 70% ethanol, fractionated by XAD-4 column chromatography with mixture solvent of methanol and water, and utilized for hypoglycemic effect assay. Significant insulin sensitizing activities of MRC extracts were observed in 3T3-L1 adipocytes, giving MRC extracts with 1 ng/mL insulin reach glucose uptake level increased by 50 ng/mL of insulin alone. MRC methanol extracts of 20, 40, 60, and 80% suppressed ${\alpha}-glucoamylase$ activity in vitro. Peak serum glucose levels and area under curve were lower in Sprague Dawley male rats treated with MRC ethanol extract than those treated with cellulose in oral glucose tolerance test using 2 g dextrin/kg body weight. These data suggest MRC extracts contain effective insulin -sensitizing and ${\alpha}-glucoamylase-suppressing$ compounds for hypoglycemic activity.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.

• Nutrition Research and Practice
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• v.5 no.6
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• pp.533-539
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• 2011

Metabolic alterations including postprandial hyperglycemia have been implicated in the development of obesity-related diseases. Xylose is a sucrase inhibitor suggested to suppress the postprandial glucose surge. The objectives of this study were to assess the inhibitory effects of two different concentrations of xylose on postprandial glucose and insulin responses and to evaluate its efficacy in the presence of other macronutrients. Randomized double-blind cross-over studies were conducted to examine the effect of D-xylose on postprandial glucose and insulin response following the oral glucose tolerance test (OGTT). In study 1, the overnight-fasted study subjects (n = 49) consumed a test sucrose solution (50 g sucrose in 130 ml water) containing 0, 5, or 7.5 g D-xylose powder. In study 2, the overnight-fasted study subjects (n = 50) consumed a test meal (50 g sucrose in a 60 g muffin and 200 ml sucrose-containing solution). The control meal provided 64.5 g of carbohydrates, 4.5 g of fat, and 10 g of protein. The xylose meal was identical to the control meal except 5 g of xylose was added to the muffin mix. In study 1, the 5 g xylose-containing solutions exhibited significantly lower area under the glucose curve (AUCg) and area under the insulin curve (AUCi) values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P < 0.0001), 0-60 min (P < 0.0001, P < 0.0001), 0-90 min (P < 0.0001, P < 0.0001) and 0-120 min (P = 0.0071, P = 0.0016). In study 2, the test meal exhibited significantly lower AUCg and AUCi values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P = 0.0005), 0-60 min (P = 0.0002, P = 0.0025), and 0-90 min (P = 0.0396, P = 0.0246). In conclusion, xylose showed an acute suppressive effect on the postprandial glucose and insulin surges.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.714-722
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• 2009

The principal objective of this study was to determine the effects of leucine on body weight reduction in high fat diet-induced overweight rats. To induce overweight, six-month-old male Sprague-Dawley rats (n = 80) were divided into 8 groups; one group of 10 rats was fed on a normal fat diet and the remaining 70 rats were fed on a high-fat diet (40% of energy as fat) for 14 weeks. Then, 10 rats fed on the normal fat diet and another 10 rats fed on the high fat diet were sacrificed to identify overweight induction. The remaining 60 rats were divided randomly into 6 groups according to body weight and fed on one of the diets with different dietary fat levels (9.6% or 40% of energy as fat) and leucine levels (0, 0.6 or 1.2 g/kg BW) for the following 5 weeks of experiments. The body weight loss in the Leu-administered groups (0.6 g, 1.2 g/kg BW) was significantly higher than those of Leu non-administered groups. The perirenal fat pad weights in the Leu-administered groups were significantly lower than those of the Leu non-administered groups. Of the hepatic enzymes, glucose-6-phosphate dehydrogenase (G6PDH) activities were reduced significantly in the Leu-administered groups than in the Leu non-administered groups. With the oral glucose tolerance test (OGTT), the incremental areas under the curve of the glucose response (IAUC) of the Leu-administered groups were significantly lower than those of the Leu non-administered groups. The fasting glucose concentration and HOMA-IR of the Leu-administered groups were significantly lower than those of the Leu non-administered groups. In conclusion, the results of this study suggest that one of the possible mechanisms of leucine in the observed body weight reduction might involve the inhibition of lipogenic enzyme activities such as glucose-6-phosphate dehydrogenase, rather than the activation of lipolysis enzymes. Additionally, leucine adminstration resulted in improved glucose metabolism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1576-1584
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• 2013

This study is carried out to assess the relative effects of different doses of dietary glucose or fructose on non-alcoholic fatty liver disease (NAFLD) and hepatic metaflammation in a rodent model of type 2 diabetes. KK/HlJ male mice were fed experimental diets as follows: 1) control (CON), 2) moderate glucose (MG, 30% of total calories as glucose), 3) high glucose (HG, 60% of total calories as glucose), 4) moderate fructose (MF, 30% of total calories as fructose), and 5) high fructose (HF, 60% of total calories as fructose) for three weeks. Food intake was not affected by treatments. Compared with HF, HG not only increased serum fasting glucose and area under the curve during oral glucose tolerance test, but also decreased the levels of serum insulin and adiponectin. It indicated that glucose control was complicated via high glucose intake. High fructose treatment led to increased triglyceride in the serum and liver. In comparison to HG, high fructose diet activated NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome consisting of apoptosis-associated speck-like protein containing a CARD (ASC), NLRP3 and caspase 1, which increases interleukin (IL)-$1{\beta}$ maturation and secretion. The activation of NLRP3 inflammasome was accompanied by increased levels of tumor necrosis factor alpha (TNF-${\alpha}$) and IL-6. However, the expression of NLRP3 inflammasome components and pro-inflammatory cytokines did not differ between CON and HG. These data suggested that dietary fructose triggers hepatic metaflammation accompanied by NLRP3 inflammasome activation and has deleterious effects on NAFLD.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.2
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• pp.267-272
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• 2017

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.1
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• pp.67-76
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• 2002

Objective: To assess the difference of baseline hormonal status and pathophysio logy, and confirm the risk factors for long term complication according to Body Mass Index in women with polycystic ovary syndrome. Materials and Methods: Serum level of LH, FSH, Estradiol, Prolactin, Testosterone, DHEA-S, fasting insulin were measured and 100 gm oral glucose tolerance test and endometrial biopsy were performed in total 75 chronic anovulation patients and 20 normal cycling infertility patients. 95 evaluated patients were divided into 3 groups including patients with chronic anovulation having BMI below 25, BMI beyond 25.1, normal cycling infertility patients, Group 1 (n=39), Group 2 (n=36), Group 3 (n=20), respectively. Statistical analysis was performed respect to relationship between BMI and measured hormone level, sum of glucose level during 100 gm OGTT, insulin resistance using t-test, ANOVA test, Post Hoc test, Mann-Whitney test. p<0.05 was considered as statistically significant. Results: Serum LH level and LH/FSH ratio was significantly higher in Group 1, compared than Group 2 or 3 (p<0.05), BMI and LH, LH/FSH ratio was negatively correlated (r=-0.351, r=-0.318). There was no significant difference according to BMI in FSH, testosterone, estradiol, prolactin, DHEA-S level. Fasting insulin and sum of glucose level during 100 gm OGTT were significantly higher in Group 2 compared than Group 1 or Group 3 (p<0.05), there was no significant difference between Group 1 and Group 3. Insulin resistance was more frequently identified in Group 2 compared than Group 1 (p=0.001). Conclusions: BMI and LH, LH/FSH ratio were negatively correlated, so clinical significance of LH, LH/FSH ratio in diagnosis of PCOS may be attenuated by increasing body weight. Overweight patients with chronic anovulation may be the risk group for developing insulin resistance, hyperinsulinemia, glucose intolerance, later type 2 DM. Hyperinsulinemia may operate mainly in overweight chronic anovulation patients in development of hyperandrogenism.

• Journal of Food Hygiene and Safety
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• v.28 no.2
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• pp.152-157
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• 2013

We evaluated the anti-diabetic effects of Isaria tenuipes in diabetes mellitus type 2. For the experiments, the diabetic animal model OLETF rats were divided to 4 groups: Isaria tenuipes was administered mixed with the high fat diet 45% at dose levels of 0.0%, 0.1%, 1.0%, and 5.0% for 4 weeks. All animals have free access to water and high fat diet 45%. The diabetic clinical markers, including clinical signs, body weight and food intake, organ weights, blood glucose level, insulin level and HOMA-IR index, oral glucose tolerance test, GLUT4 mRNA and protein were measured at a time. After administration for 4 weeks, the blood glucose levels, insulin levels and HOMA-IR index of test groups were decreased compared with control group in dose-dependent manner. The body weight and diet consumptions were reduced in control group at 4 weeks. The treatments of Isaria tenuipes also showed high expression of GLUT4 mRNA and protein in the muscle of OLETF rats. The results suggest that Isaria tenuipes has anti-hyperglycemic effect attenuating blood glucose in the animal model of type 2 diabetes and might be useful as a functional diet for human diabetic diseases.

• The Journal of Korean Medicine
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• v.33 no.3
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• pp.184-199
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• 2012

Objectives: There is a steady increase in the prevalence of obesity worldwide and obesity is often accompanied by inflammation. Although much emphasis has been placed on the adipose tissue inflammation in obesity, a study with herbal medicine is few. This study aimed to investigate the antidiabetic and anti-inflammatory effect of a complex herbal medicine (CHM) composed of Cornus officinalis, Dioscorea rhizoma, Aurantii fructus, and Mori Foliumon on obese type 2 diabetes mice. Methods: Type 2 diabetes mellitus and obesity were induced by Surwit's high fat, high sucrose diet for 8 weeks. Mice were divided into ND (normal diet, n=10), HFD (high fat and high sucrose diet, n=10), CHM (high fat and high sucrose diet with complex herbal medicine, n=10) and Met (high fat and high sucrose diet with metformin, n=10) groups. The body weight, fructosamine and OGTT (oral glucose tolerance test) were measured. After 8 weeks the blood samples of all mice were taken from the heart, and lipid profiles were measured. Epididymal fat pad, histological size of the adipocyte tissue and liver weights were measured. Inflammatory markers such as leptin and adipocyte tissue macrophage were measured to evaluate the effect of CHM on adipocyte tissue inflammation. Results: Compared with the HFD group, there was an improvement in OGTT and epididymal fat decreased in the CHM group. White adipocyte size and adipocyte tissue macrophage decreased in CHM group. Conclusions: These results suggest that CHM has antidiabetic and anti-inflammatory effects in high fat, high sucrose diet induced obese mice.