• Journal of Nutrition and Health
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• v.54 no.6
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• pp.603-617
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• 2021

Purpose: This study was carried out to investigate the effect of amaranth seed extracts on glycemic regulation in HepG2 cells. The 80% ethanol extracts of amaranth seeds were used to evaluate α-amylase and α-glucosidase activities, cell viability, glucose uptake and messenger RNA (mRNA) expression levels of acetyl-CoA carboxylase (ACC), glucose transporter (GLUT)-2, GLUT-4, insulin receptor substrate (IRS)-1 and IRS-2. Methods: The samples were prepared and divided into 4 groups, including germinated black amaranth (GBA), black amaranth (BA), germinated yellow amaranth (GYA) and yellow amaranth (YA). Glucose hydrolytic enzyme, α-amylase and α-glucosidase activities were examined using a proper protocol. In addition, cell viability was measured by MTT assay. Glucose uptake in cells was measured using an assay kit. The mRNA expression levels of ACC, GLUT-2, GLUT-4, IRS-1 and IRS-2 were measured by reverse transcription polymerase chain reaction. Results: The inhibitory activities of α-amylase and α-glucosidase were highly observed in GBA, followed by BA, GYA and YA. Similar results were observed for glucose. The GBA effect was similar compared to the positive control group. The mRNA expression levels of ACC, GLUT-2, GLUT-4, IRS-1, and IRS-2 were significantly increased. The potential hypoglycemic effects of amaranth seed extracts were observed due to the increase in glucose metabolic enzyme activity, and glucose uptake was mediated through the upregulation of ACC, GLUT-2, GLUT-4, IRS-1, and IRS-2 expression levels. Conclusion: Our findings suggest that the amaranth seed is a potential candidate to prevent a diabetes. The present study demonstrated the possibility of using amaranth seeds, especially GBA and BA for glycemic control.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.2
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• pp.93-101
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• 2022

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.324-330
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• 2015

In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.417-424
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• 2019

The aim of this study is to investigate the effect of Lespedeza maximowiczii var. tricolor Nakai (LMTN) on glucose metabolism. LMTN extract significantly enhanced the glucose uptake and lipid accumulation in 3T3-L1 adipocytes compared with control. Also, LMTN extract in 3T3-L1 adipocytes significantly increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ, insulin receptor substrate-1, and glucose transporter (GLUT)4. The regulatory effect on glucose uptake or insulin signal transduction of LMTM extract was lower than troglitazone or pinitol such as the positive control, but increased PPARγ activation. Additionally, LMTM extract has an insulin-mimetic effect. In db/db mice, LMTN extract (250 mg/kg BW) significantly reduced water and food intake, blood glucose, and level of plasma triglyceride and total cholesterol. Furthermore, the expression of PPARã and GLUT4 mRNA in adipose or muscle tissue effectively was increased by oral treatment of LMTN extract. Thus, our results suggest that LMTN extract improves the glucose metabolism through PPARγ and insulin-mimetic effect in 3T3-L1 adipocytes and db/db mice.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.331-337
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• 2015

Background: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. Methods: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma ($PPAR-{\gamma}$), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. Results: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG-treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, $PPAR-{\gamma}$, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. Conclusion: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice.

• Genomics & Informatics
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• v.12 no.4
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• pp.240-246
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• 2014

Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Journal of Life Science
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• v.10 no.4
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• pp.388-396
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• 2000

The effect of the traditional herbal medicine Yukmijihwangtang-Jahage(YJ) on the improvement of insulin resistance and lipid profile was studied using a model for non-insulin dependent diabetes mellitus, lean (Fa/-) and obese (fa/fa) Zucker rats. Yukmijihwangtang-Jahage feeding for 4 weeks resulted in a significant decrease in the concentration of plasma triglyceride in both lean and obese Zucker rats. Furthermore, Yukmijihwangtang-Jahage markedly decreased both plasma cholesterol and fasting plasma insulin, and significantly decreased the postprandial glucose level at 30 min during oral glucose tolerance test in obese Zucker rats. Although there was no statistical significance, the crude glucose transporter 4 protein level of Yukmijihwangtang-Jahage dieted obese rats tended to increase when compared to that of obese control rats. Therefore, the present results suggested that Yukmijihwangtang-Jahage may be useful in prevention and improvement of metabolic disorders characterized by hyperinsulinemia states such as non-insulin dependent diabetes mellitus, syndrome X and coronary artery disease.

• Journal of Applied Biological Chemistry
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• v.64 no.1
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• pp.89-96
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• 2021

The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

• 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.