• Korean Journal of Exercise Nutrition
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• v.16 no.2
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• pp.65-71
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• 2012

Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.

• 한국인삼전략화협의회:학술대회논문집
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• v.2003 no.09
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• pp.77-88
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• 2003

"Ginseng (Panax ginseng C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years, and a number of health claims are made for it. Modern therapeutic claims for ginseng refer to vitality, immune function, cancer, cardiovascular diseases, diabetes and sexual function. These claims are mostly based on uncontrolled or non-randomized studies. Among modern therapeutic claims, however, therapeutic effects for diabetes can reasonably be accepted. Following experiment was done recently in our lab: this study was designed to compare the antidiabetic activities between Ginseng Radix Alba (GRA), Ginseng Radix Rubra (GRR) and Panax Quinquefoli Radix (PQR) in multiple low dose (MLD) streptozotocin (STZ) (20mg/kg i.p injection for 5 days) induced diabetic rats. In the glucose tolerance test, 500mg/kg of each ginseng ethanol extract was admoinistered intraperitoneally 30min before glucose challenge. While GRA failed to lower blood glucose level, GRR and PQR both significantly prevented the hyperglycemia when compared with the control group. In the MLD STZ-induced diabetic rats, 300 mg/kg of each ginseng ethanol extract was administered intraperitoneally for 2 weeks. Plasma glucose and insulin levels were markedly improved in all treatment groups. While GRR showed the highest antidiabetic activity, and GRA and PQR revealed somewhat equipotent antidiabetic activities, but less than that in GRR-treated group as for as blood parameters and diabetic symptoms such as polydipsia are concerned. Blood glucose levels were closely associated with plasma insulin levels, and this result may suggest that ginseng ethanol extracts showed the activity to enhance insulin secretion as well as preventing destruction of pancreatic islet cells. To elucidate the relationship between antidiabetic activity and ginsenoside profiles, seven major ginsenoside were quantified by HPLC. We figured out the fact that protopanaxatriol (PPT) : proptopanaxadiol (PPD) ratio might play an important role in its hypoglycemia effects."

• YAKHAK HOEJI
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• v.51 no.5
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• pp.307-312
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• 2007

Thiazolidinediones (TZDs) induce insulin sensitization through the activation of PPAR${\gamma}$. However, the undesirable effect such as weight gain was observed. The purpose of this study was to find out an herbal drug that could reduce the side effects of pioglitazone. Among herbal formula that we have searched, oryung-san (OR) inhibited the differentiation of preadipocytes and did not affect on glucose uptake in 3T3-L1 adipocytes. In vitro, glucose uptake assay and Oil Red-O staining in 3T3-L1 adipocytes were conducted. In vivo, pioglitazone (PIO, 30 mg/kg), oryung-san (OR, 300 mg/kg), or pioglitazone co-administered with oryung-san (PIO+OR) were administered orally for 7 weeks in high fat diet (HFD) fed ICR mice and measured the body weight and blood glucose level every week. PIO+OR group significantly reduced body weight gain, triglyceride, and total cholesterol compared to PIO group. In addition, PIO+OR group showed a significant reduction of plasma glucose level (72%) compared to HFD control group. Insulin levels in PIO+OR group was also markedly decreased by 85% and 41% compared to HFD control and PIO group, respectively. Diameter of white adipocytes was decreased in the PIO+OR group compared to that in PIO group. Moreover, PIO+OR group reduced expression of PPAR${\gamma}$ and SREBP1a compared to PIO group. Taken together, oryung-san can improve side effects of pioglitazone, such as weight gain and edema, and shows a synergistic effect in plasma insulin levels.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1055-1062
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• 2012

Two SNPs, i.e. L127V and T172M, of bovine growth hormone (GH) causing the presence of GH gene haplotypes A, B, and C was previously shown to alter intramuscular fatty acid (FA) composition in Japanese Black (JB) heifers. To determine the SNP effect on somatotropic hormone concentration and lipogenesis, we measured plasma GH, insulin, and insulin-like growth factor-1 (IGF-1) concentrations. We also measured mRNA levels of fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), and sterol regulatory element binding proteins-1 (SREBP-1) and FA composition in diaphragm tissues. Heifers with genotype CC had the lowest plasma insulin concentration and FASN and SCD mRNA levels among genotypes. FASN mRNA levels in haplotype A tended to positively correlate with saturated FA (SFA) content and negatively correlated with C18:2 and unsaturated FA (USFA) contents. SCD mRNA levels in haplotype A positively correlated with monounsaturated FA (MUFA) contents and negatively correlated with C18:0 content. They also tended to positively correlate with C16:1, C18:1, and USFA contents and USFA/SFA ratio and negatively correlate with SFA content. Taken together, GH gene polymorphism affects the lipogenic genes expression levels and their relationships with fatty acid compositions in diaphragm tissues of JB heifers at 31 months of age.

• Korean Journal of Pharmacognosy
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• v.43 no.4
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• pp.308-315
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• 2012

Opuntia humifusa known as the Eastern prickly pear have been used as a treatment of burns, diarrhea, asthma, rheumatism, gonorrhea, and diabetes in alternative medicine. O. humifusa is widely cultivated in the middle and southern provinces of Korea and distributed in North America. The aim of this study is to investigate anti-diabetic effect of O. humifusa stem (OHS) water or 80% MeOH extract using 3T3-L1 adipocytes and db/db mice animal models. OHS 80% MeOH extract at a dose of $250{\mu}g/ml$ significantly increased the glucose uptake and lipid accumulation compared with the control in 3T3-L1 adipocytes. Blood glucose, plasma total cholesterol and triglyceride levels were significantly reduced by oral treatment of OHS 80% MeOH extract (200 mg/kg BW) for 6 weeks in db/db mice. Also, the oral treatment of OHS 80% MeOH extract slightly changed the plasma insulin and insulin resistance levels in db/db mice, but were no significance in comparison to control. Glucose transporter(GLUT)4 expressions of adipose tissue and muscle were significantly increased more than that in the control. Therefore, these results suggest that OHS 80% MeOH extract inhibits the blood glucose level through regulation of lipid profile, insulin resistance, and GLUT4 expression in db/db mice and its diabetic effect is effective more than water extract.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.239-243
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• 2014

Background: To investigate the antidiabetic effects of hydrolyzed ginseng extract (HGE) for Korean participants in an 8-wk, randomized, double-blinded, placebo-controlled clinical trial. Methods: Impaired fasting glucose participants [fasting plasma glucose (FPG) ${\geq}5.6mM$ or < 6.9mM who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 23 participants were randomly divided into either the HGE (n = 12, 960 mg/d) or placebo (n = 11) group. Outcomes included measurements of efficacy (FPG, postprandial glucose, fasting plasma insulin, postprandial insulin, homeostatic model assessment-insulin resistance, and homeostatic model assessment-${\beta}$) and safety (adverse events, laboratory tests, electrocardiogram, and vital signs). Results: After 8 wk of HGE supplementation, FPG and postprandial glucose were significantly decreased in the HGE group compared to the placebo group. No clinically significant changes in any safety parameter were observed. Our study revealed that HGE is a potent antidiabetic agent that does not produce noticeable adverse effects. Conclusion: HGE supplementation may be effective for treating impaired fasting glucose individuals.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.3
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• pp.346-351
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• 2002

The effect of fetal number (single or twin) on plasma concentrations of progesterone, estradiol $17{\beta}$, cortisol, prolactin, growth hormone, triiodothyronine, thyroxine and insulin around parturition (periparturient period) were studied on ten $Alpine{\times}Beetle$ crossbred goats in their first to third lactation. The hormone profiles were studied on days -20, -15, -10, -5, -4, -3, -2, -1 prior to kidding and on day 0 and +1, +2, +3, +4, +5, +10, +15, +20 days postkidding. Plasma progesterone levels were significantly (p<0.01) higher in twin bearing goats comparison to single bearing goats during all the days of sampling. The decline in progesterone concentration from day 20 to day 1 before kidding was 56% in twin and 42% in single bearing goats. In single bearing goats plasma estradiol $17{\beta}$ was significantly (p<0.01) higher during prekidding days compared to twin bearing goats. The level of estradiol $17{\beta}$ was highest on the day of kidding in both the groups. The plasma prolactin level in twin bearing goats from day 10 to day 1 prepartum was higher as compared to single fetus bearing goats. However there was abrupt increase in prolactin level on the day of kidding in both the groups. The plasma growth hormone levels were significantly (p<0.01) higher in twin compared to single bearing goats. On the day of kidding growth hormone levels were significantly (p<0.01) higher in twin as compared to single bearing goats (1.40 vs. 0.95 ng/ml). In twin bearing goats plasma cortisol values from day 5 till the day of kidding remained elevated and the levels on the day of kidding was significantly highest in both the groups. The levels of triiodothyronine ($T_3$) were significantly higher (p<0.01) during all the periods of sampling in single compared to twin bearing goats. Plasma thyroxine ($T_4$) was significantly (p<0.01) lower in twin compared to single bearing goats. In single bearing goats plasma insulin levels were significantly (p<0.01) higher than twin bearing goats during prepartum period however during post partum period the levels in both the groups remained similar. It can be concluded that number of fetuses is having significant influence on the hormone profile during periparturient period.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.9
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• pp.1210-1218
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• 2000

Four experiments were conducted to evaluate the effect of temperature and humidity on biochemical indices of Arbor Acres broilers at different weeks of age. The alkaline phosphatase (AKP), acid phosphatase (ACP), lactic dehydrogenase (LD), creatine kinase (CK), plasma glucose (Glu), calcium (Ca), potassium (K), chloride (Cl), urea nitrogen (UN), uric acid (UA), plasma thyroxin (T4), triiodothyronine (T3) and insulin levels were determined in all the four experiments. In experiment 1, the plasma Glu, LD and CK levels were increased by heat exposure ($35{^{\circ}C}$ and 35, 60, or 85% RH, 2 h) and this effect was aggravated by longer exposure (24 h). No significant changes (p>0.05) were found in Ca concentration, activity of AKP and ACP. In experiment 2, temperature (10, 20, 30, $33{^{\circ}C}$) had significant effect on the levels of K, Cl, UN, UA levels and the activity of LD (p<0.01), but had no significant influence on the activity of CK (p>0.05). The UN, UK and LD levels were elevated by low temperature $(10{^{\circ}C})$ (p<0.01), Cl content was increased by high temperature ($(33{^{\circ}C})$ (p<0.01), and K level was decreased by high ($(33{^{\circ}C})$ or low $(10{^{\circ}C})$ temperature and increased by medium temperature $(30{^{\circ}C})$ (p<0.01). The humidity (35, 85% RH) only had significant effect on Cl concentration which was decreased by high humidity (p<0.01). In experiment 3, the result showed that only the LD and CK activity were significantly increased (p<0.01) by high temperature (7, 24, 28, $32{^{\circ}C}$) or high humidity (35, 85% RH). Temperature and humidity had no significant effect on K, Cl, UA, UN and Glu levels (p>0.05). In experiment 4 (24, 27, 30, $33{^{\circ}C}$; 30, 45, 60, 75, 90% RH), plasma T3 level was declined by high temperature $(33{^{\circ}C})$, and this phenomena disappeared in birds under high temperature and high humidity environment. T4 concentration in plasma was not affected by temperature (p>0.05), but was increased by high or low humidity (p<0.01). Neither temperature nor humidity had significant effect on plasma insulin concentration (p>0.05). The results of the four experiments suggested that broilers at different growth periods might have different thermal requirements and would response differently to heat exposure. The plasma biochemical indices themselves had big variation; the reaction of the indices to thermal exposure treatment differed with the age of broilers. The big variation of biochemical indices themselves might cover the response of indices to temperature and humidity treatments.

• Proceedings of the Ginseng society Conference
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• 2007.12a
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

• Advances in Traditional Medicine
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• v.1 no.2
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• pp.14-20
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• 2000

This study was designed to investigate the effect of dietary Platycodon grandiflorum on plasma glucose and lipid metabolism in $KK-A^y$ mice and STZ-induced diabetic rats. Both plasma triglyceride and plasma cholesterol levels in STZ-induced diabetic rats were significantly decreased by dietary Platycodon grandiflorum feeding for 4 weeks compared to those of control rats, but there were no marked differences in $KK-A^y$ mice. However, for plasma glucose values, Platycodon grandiflorum feeding resulted in a significant decrease in both STZ-induced diabetic rats and $KK-A^y$ mice. Also, dietary Platycodon grandiflorum slightly decreased the postprandial glucose level at 30 and 60 mins during oral glucose tolerance test in $KK-A^y$ mice. Although there was no statistical significance, the fasting plasma insulin levels of Platycodon grandiflorum dieted $KK-A^y$ mice tended to decrease when compared to that of control mice. Therefore, the present results suggested that dietary Platycodon grandiflorum may have a beneficial effect on preventing hypercholesterolemia and hyperlipidemia.