• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.191-197
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• 1984

A further purified fraction (D-O-ANa) was obtained from DPG 3-2 fraction of Ginseng Radix by complete removal of saponins, nucleosides, nucleic acid bases, amino acids, and sugars. D-O-ANa - induced insulin release was investigated to compare with that of DPG 3-2 and other isolated components. Among the sub fractions of DPG 3-2, D-O-ANa exhibited the most potent release of insulin with or without high concentrations of glucose, and it particularly enhanced the second phase of glucose-induced insulin release. DGP 3-2 potentiated significantly the glucose-induced insulin release from the isolated islets of diabetic mice at increasing concentrations of extracellular calcium ions (0.16 - 2.5 mM). A definite relationship was found between calcium $(^{45}Ca)$ uptake and insulin release. Ginsenoside $(G)-Rb_1\;and\;G-Rg_1$ did not enhance the glucose-induced insulin release. The effect of ginseng saponins was blocked by glucose (16.7 mM), being distinctly different from the glucose-potentiated effect of DPG 3-2. The insulin release effect of $G-Rg_1$ was unaffected by the presence or absence of extracellular $Ca^{2+}$ and theophylline. Adenosine also increased insulin release from isolated islets, but had no effect on perfused rat pancreas. Arginine stimulated insulin release less evidently than D-O-ANa, though arginineand adenosine-induced glucagon releases were more remarkable. In conclusion, D-O-ANa appears to be a major fraction in insulin release activity of ginseng and its mode of action may be related to $Ca^{2+}$ ion uptake. This physiological mechanism was distinct from that of the abnormal release induced by ginseng saponins.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.351-358
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• 2016

Background: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. Methods: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry. Results: Rb1 and CK suppressed ER stress by dephosphorylation of $IRE1{\alpha}$ and PERK, thereby reducing TXNIP-associated NLRP3 inflammasome activation in adipose tissue. As a result, Rb1 and CK inhibited IL-$1{\beta}$ maturation and downstream inflammatory factor IL-6 secretion. Inflammatory molecules induced insulin resistance by upregulating phosphorylation of insulin receptor substrate-1 at serine residues and impairing insulin PI3K/Akt signaling, leading to decreased glucose uptake by adipocytes. Rb1 and CK reversed these changes by inhibiting ER stress-induced inflammation and ameliorating insulin resistance, thereby improving the insulin IRS-1/PI3K/Akt-signaling pathway in adipose tissue. Conclusion: Rb1 and CK inhibited inflammation and improved insulin signaling in adipose tissue by suppressing ER stress-associated NLRP3 inflammation activation. These findings offered novel insight into the mechanism by which Rb1 and CK ameliorate insulin resistance in adipose tissue.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.56-63
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• 2007

Insulin stimulates the fusion of intracellular vesicles containing glucose transporter 4 (GLUT4) with plasma membrane in adipocytes and muscle cells. Here we show that adipocyte differentiation results in enhanced insulin sensitivity of glucose uptake. On the other hand, glucose uptake in response to platelet-derived growth factor (PDGF) stimulation was markedly reduced by adipocyte differentiation. Expression level of insulin receptor and caveolin-1 was dramatically increased during adipocyte differentiation. Adipocyte differentiation caused :ilightly enhanced activation of acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) by insulin stimulation. However, activation of Akt by PDGF stimulation was largely reduced. Activation of ERK was not detected in both fibroblasts and adipocytes after stimulation with insulin. PDGF-dependent activation of ERK was reduced by adipocyte differentiation. Insulin-dependent glucose uptake was abrogated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, in both fibroblasts and adipocytes. Also disassembly of caveolae structure by $methyl-\beta-cyclodextrin$ caused impairment of Akt activation and glucose uptake. Finally, insulin receptor, Akt, SH2-domain-containing inositol 5-phosphatase 2 (SHIP2), and regulatory subunit of PI3K are localized at lipid raft domain and the translocation was facilitated upon insulin stimulation. Given these results, we suggest that lipid raft provide proper site for insulin action for glucose uptake.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.331-344
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• 1990

What makes glucose transport function sensitive to insulin in one cell type such as adipocyte, and insensitive in another such as liver cells is unresolved question at this time. Recently it is known that insulin stimulates glucose transport in adipocytes largely by redistributing transporter from the storage pool that is included in a low density microsomal fraction to plasma membrane. Therefore, insulin sensitivity may depend upon the relative distribution of gluscose transporters between the plasma membrane and in an intracellular storage compartment. In hepatocytes, the subcellular distribution of glucose transporter is less well documented. It is thus possible that the apparent insensitivity of the hepatocyte system could be either due to lack of the constitutively maintained, intracellular storage pool of glucose transporter or lack of insulin-mediated transporter translocation mechanism in this cell. In this study, I examined if any intracellular glucose transporter pool exists in hepatocytes and this pool is affected by insulin. The results obtained summarized as followings: 1) Distribution of subcellular fractions of hepatocyte showed that there are $24.9{\pm}1.3%$ of plasma membrane, $36.9{\pm}1.7%$ of nucleus-mitochondria enriched fraction, $23.5{\pm}1.2%$ of lysosomal fraction, $9.6{\pm}1.0%$ of high density microsomal fraction and $4.9{\pm}0.5%$ of low density microsomal fraction. 2) In adipocyte, there were $29.9{\pm}2.6%$ of plasma membrane, $19.4{\pm}1.9%$ of nucleus-mitochondria enriched fraction, $26.7{\pm}1.8%$ of high density microsomal fraction and $23.9{\pm}2.1%$ of low density microsomal fraction. 3) Surface labelling of sodium borohydride revealed that plasma membrane contaminated to lysosomal fraction by $26.8{\pm}2.8%$, high density microsomal fraction by $8.3{\pm}1.3%$ and low density microsomal fraction by $1.7{\pm}0.4%$ respectively. 4) Cytochalasin B bound to all of subcellular fractions with a Kd of $1.0{\times}10^{-6}M$. 5) Photolabelling of cytochalasin B to subcellular fractions occurred on 45 K dalton protein band, a putative glucose transporter and D-glucose inhibited the photolabelling. 6) Insulin didn't affect on the distribution of subcellular fractions and translocation of intracellular glucose transporters of hepatocytes. 7) HEGT reconstituted into hepatocytes was largely associated with plasma membrane and very little was found in low density microsomal fraction which equals to the native glucose transporter distribution. Insulin didn't affect on the distribution of exogeneous glucose transporter in hepatocytes. From the above results it is concluded that insulin insensitivity of hepatocyte may due to lack of intracellular storage pool of glucose transporter and thus intracellular storage pool of glucose transporter is an essential feature of the insulin action.

• Journal of Nutrition and Health
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• v.54 no.3
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• pp.247-261
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• 2021

Purpose: This study was conducted to identify the association between insulin resistance and the major dietary patterns of Korean adults. Methods: This study used data from the 2015 Korea National Health and Nutrition Examination Survey. The subjects were 2,276 adults aged 19 to 64 years old. Based on the food frequency questionnaire data, 112 food items were reclassified into 30 food groups. The principal component analysis method was applied to identify major dietary patterns. We used homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) value as indicators of insulin resistance. The association between major dietary patterns and insulin resistance was investigated using logistic regression analysis. Results: Three major dietary patterns were identified and assigned descriptive names based on the food items with high loadings: 'healthy Korean meal pattern', 'western meal pattern', and 'white rice, alcohol, meat pattern'. As the 'white rice, alcohol, meat pattern' score increased, significant increasing trends for fasting glucose concentration and HOMA-IR and a significant decreasing trend for QUICKI were observed after adjusting for age and sex. The odds ratio of insulin resistance according to the 'healthy Korean meal pattern' and the 'western meal pattern' were not statistically significant. the 'white rice, alcohol, meat pattern' showed a significant positive association with the risk of insulin resistance after adjusting for covariates. Conclusion: These results suggest that the 'white rice, alcohol, meat pattern' is positively associated with the risk of insulin resistance. The white rice, alcohol, meat pattern was related to the high consumption of alcohol together with rice or meat. This pattern was also associated with the high intake of sodium and low intakes of vitamin C, calcium, potassium, and dietary fiber. To confirm the association, further longitudinal studies are required.

• Journal of Embryo Transfer
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• v.23 no.3
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• pp.189-195
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• 2008

The objective of this study is to investigate the changes in concentrations of leptin and insulin in serum of Korean cattle (Hanwoo) with reproductive disorders and to examine the relationship among leptin, insulin, and body condition score (BCS). The concentration of leptin in serum of pregnant Hanwoo showed insignificant difference from that in serum of Hanwoo with reproductive disorder, such as repeat breeding, follicular cyst, corpus luteum cyst, ovarian atrophy, and feeble estrus (p>0.05). However, the concentrations of leptin and insulin in serum were changed with different BCS value. In emaciated Hanwoo (BCS $2.0\sim2.9$), they were significantly decreased compared to BCS $3.0\sim3.4$ (p<0.05). The leptin showed different genotypes with different BCS value. In BCS $2.0\sim2.9$, C/T genotype was expressed (83.3%) more than C/C (16.7%) or T/T (0%) genotype, whereas C/C genotype was expressed (62.5%) more than C/T (25.0%) or T/T (12.5%) genotype in BCS $3.5\sim4.0$. The insulin concentration in follicular fluid obtained from ovary with follicular cyst which has follicles having diameter of $25\sim40 mm$ was significantly higher (p<0.05) than those in normal follicle fluid which has follicles having diameter of $3\sim10 mm$. These results showed that concentration of leptin and insulin in serum were related to BCS value and follicular size and suggest that the changes in concentration of leptin and/or insulin in serum could be a potent biomarker for diagnosis of bovine reproductive disorder.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.4
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• pp.131-138
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• 2013

Insulin resistance and pancreatic beta cell dysfunction have been established as being related to the diabetes. Lately, what is emphasizing is that those have been shown as something related to the metabolic syndrome and cardiovascular disease. Homeostasis model assessment (HOMA), simple index is calculated on blood levels of fasting glucose and insulin. And HOMA has been widely validated and applied for insulin resistance and pancreatic beta cell dysfunction. We also assessed the factors relative to insulin resistance and ${\beta}$ cell function determined by HOMA. The data from the 2010 Korean National Health and Nutrition Examination Survey were used. Analysis was done for 3,465 nondiabetic subjects (male 1,357, female 2,108). At baseline, anthropometric measurements were done and fasting glucose, insulin, lipid (Total cholesterol, HDL cholesterol, LDL cholesterol and Triglycerides) profiles were measured. HOMA-insulin resistance (HOMA-IR) and beta cell function (HOMA ${\beta}$-cell) were calculated from fasting glucose and insulin levels. In male, the value of HOMA-IR and HOMA ${\beta}$-cell was the highest among 30's and decreased as the age increased. In female, the value of HOMA-IR increased with age, while HOMA ${\beta}$-cell decreased. High HOMA-IR and low HOMA ${\beta}$-cell were associated with the highest value of fasting glucose and systolic blood pressure. Low HOMA-IR and high HOMA ${\beta}$-cell showed the lowest concentration of fasting glucose and the highest concentration of HDL cholesterol. High HOMA-IR and high HOMA ${\beta}$-cell were connected with BMI, Total cholesterol, LDL cholesterol, and Triglycerides. There was a negative correlation between HOMA ${\beta}$-cell and age. The correlation coefficients of HOMA-IR and HOMA ${\beta}$-cell showed the highest value among weight, BMI and WC.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.83-90
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• 1997

Aim of this study was to investigate if pancreatic polypeptide (PP) reduced the insulin action via the intra-pancreatic cholinergic nerves in the isolated rat pancreas. The pancreas was isolated from rats and perfused with intra-arterial infusion of modified Krebs-Henseleit solution containing 2.5 mM glucose at a flow rate of 1.2 ml/min. Simultaneous intra-arterial infusion of insulin (100 nM) resulted inpotentiation of the pancreatic flow rate and amylase output which were stimulated by cholecystokinin (CCK, 14 pM). These potentiating actions of insulin on the CCK -stimulated pancreatic exocrine secretion were completely abolished by administration of rat PP. Vesamicol, a potent inhibitor of vesicular acetylcholine storage, and tetrodotoxin (TTX) also significantly reduced the combined actions of insulin and CCK. Administration of carbamylcholine, an acetylcholine agonist, completely restored the vesamicol- or TTX-induced inhibition of the potentiation between insulin and CCK. Also rat PP failed to attenuate the restoring effect of carbamylcholine. Electrical field stimulation (15-30 V, 2 msec and 8 Hz) resulted in a significant increase in the pancreatic flow rate and amylase output in voltage-dependent manner. Effects of electrical field stimulation were augmented by endogenous insulin. Rat PP also suppressed the pancreatic exocrine secretion stimulated by electrical field stimulation. These observations strongly suggest that PP inhibits the potentiating actions of insulin on CCK -stimulated pancreatic exocrine secretion by suppression of the intra-pancreatic cholinergic activity in the isolated rat pancreas.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1575-1579
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• 2007

The glucose tolerance and pancreatic insulin secretion response to glucose in sheep fed on germinated sorghum grain were determined using an intravenous glucose load. Twelve male Thin Tail sheep (an Indonesian native sheep, 12 months old and 14.8 kg average body weight) were divided randomly into sorghum grain-based (S), germinated sorghum grain-based (G) and maize grain-based (C) diets. Sheep were maintained at the same daily intake levels of metabolizable energy and crude protein in the diets throughout the experimental period. After two months of the experimental conditions, each diet group was subjected to an intravenous glucose load experiment in which five doses of glucose (0, 10, 20, 40 and 80 mg/kg BW) were injected to estimate the rate of glucose removal from blood and the pancreatic insulin secretion response. For each sheep and each glucose load dose, the incremental blood serum glucose and insulin concentrations above pre-injection concentration were calculated as serum glucose and insulin response areas. At all glucose doses, sheep fed on S diet had a greater (p<0.05) glucose response area compared to those of sheep fed on G and C diets. Likewise at all glucose doses, the insulin response area was smaller (p<0.05) in sheep fed on S diet than in sheep fed on G and C diets. The glucose and insulin response areas in sheep fed on G and C diets differed slightly. It was concluded that the portion of maize grain in the ruminant ration could be substituted by germinated sorghum grain.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.125-130
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• 2005

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (p＜0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (p＜0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (p＜0.01), and it was decreased significantly by leptin treatment (p＜0.01). The glucose transport was measured under basal and $60{\mu}u/ml$ of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.